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.
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 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).
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.
Vesicare tab.p.p.o.5mg No. 30 48231
Description
5 mg tablet: round, biconvex, film-coated, light yellow in color, marked “150” and the company logo on one side. 10 mg tablet: round, biconvex, film-coated, light pink in color, marked “151” and the company logo on one side. General characteristics Absorption. Cmax is reached within 3–8 hours. The time to reach Cmax does not depend on the dose. Cmax and AUC 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 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 cytochrome P450 3A4 (CYP3A4). However, there are alternative metabolic pathways through which solifenacin can be metabolized. The systemic Cl of solifenacin is about 9.5 l/h, and the final T1/2 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 dose of 10 mg 14C-labeled solifenacin administered after 26 days, approximately 70% of the radioactivity was detected in urine and 23% in feces. 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 elderly subjects (65 to 80 years) and healthy young subjects (<55 years). The mean absorption rate, expressed as Tmax, was slightly lower and the final T1/2 was approximately 20% longer in older adults. These minor differences are not clinically significant. The pharmacokinetics of solifenacin have not been determined in children and adolescents. Floor. The pharmacokinetics of solifenacin does not depend on the gender of the patient. Race. Race does not affect the pharmacokinetics of solifenacin. Kidney failure. The AUC and Cmax of solifenacin in patients with mild to moderate renal impairment do not differ significantly from the corresponding values in healthy volunteers. In patients with severe renal failure (creatinine clearance ≤30 ml/min), exposure to solifenacin is significantly higher (increase in Cmax is about 30%, AUC is >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 (Child-Pugh score from 7 to 9), the Cmax value does not change, AUC increases by 60%, T1/2 doubles. Pharmacokinetics in patients with severe hepatic impairment have not been determined. Pharmacological studies conducted in vitro and in vivo have shown that solifenacin is a specific competitive inhibitor of muscarinic receptors, predominantly of the M3 subtype. Solifenacin has also been found to have low affinity or does not interact with other receptors and ion channels. The effectiveness of Vesicare® in doses of 5 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 next 12 weeks of treatment. The maximum effect of Vesicare® can be detected after 4 weeks. Efficiency is maintained over long-term use (at least 12 months). Before starting treatment with Vesicar®, it should be determined whether there are other causes of frequent urination (heart failure or kidney disease). If a urinary tract infection is detected, appropriate antibacterial treatment should be started. Vesicare® should be prescribed with caution to patients: - with clinically significant obstruction of the bladder outlet, leading to the risk of developing urinary retention; — with gastrointestinal obstructive diseases; - at risk of decreased gastrointestinal motility; — with severe renal (Cl creatinine ≤30 ml/min) and moderate hepatic (Child-Pugh score from 7 to 9) failure; Doses for these patients should not exceed 5 mg; - while taking a strong CYP3A4 inhibitor, such as ketoconazole; - with a hiatal hernia, gastroesophageal reflux and patients simultaneously taking medications (for example, bisphosphonates) that can cause or worsen esophagitis; - with autonomic neuropathy. Patients with rare hereditary disorders of galactose tolerance, lactase deficiency of the Lapps (Sami), glucose-galactose malabsorption should not take the drug. Solifenacin, like other anticholinergic drugs, may cause blurred vision and (rarely) drowsiness and fatigue, which may impair the ability to drive and operate machines.
Compound
Film-coated tablets 1 tablet core: solifenacin succinate 5 mg excipients: lactose monohydrate; corn starch; hypromellose 3 mPa s; magnesium stearate; purified water shell: Opadry yellow 03F12967 (hypromellose 6 mPa s; talc; macrogol 8000; titanium dioxide; iron oxide yellow) in a strip pack of 10 pcs.; in a cardboard pack 1 or 3 packs. Film-coated tablets 1 tablet core: solifenacin succinate 10 mg excipients: lactose monohydrate; corn starch; hypromellose 3 mPa s; magnesium stearate; purified water shell: Opadry pink 03F14895 (hypromellose 6 mPa s; talc; macrogol 8000; titanium dioxide; iron oxide red) in a strip pack of 10 pcs.; in a cardboard pack 1 or 3 packs.
Application
Urgent (imperative) urinary incontinence, frequent urination and urgent (imperative) urge to urinate, characteristic of patients with overactive bladder syndrome. 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 exercised when prescribing this drug to pregnant women. There is no data on the excretion of solifenacin in milk in humans. The use of Vesicare® is not recommended during breastfeeding. 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. The table below summarizes the remaining side effects reported in clinical trials of Vesicare®: Side effects Common (≥1/100, <1/10) Uncommon (≥1/1000, <1/100) Rare (≥1/10000, <1 /1000) Gastrointestinal disorders constipation, nausea, dyspepsia, abdominal pain gastroesophageal reflux disease, dry pharynx colonic obstruction, coprostasis Infections and infestations urinary tract infection Nervous system disorders drowsiness, dysgeusia (taste disturbance) Visual disorders blurred vision vision (impaired accommodation) dry eyes Disorders of the general condition fatigue, swelling of the lower extremities Disorders of the respiratory system, chest and mediastinum dry nasal cavity Disorders of the skin and subcutaneous tissue dry skin Disorders of the kidneys and urinary tract difficulty urinating urinary retention Allergic reactions were not observed during clinical trials. However, the possibility of allergic reactions should not be excluded. Pharmacological interaction Concomitant treatment of drugs with anticholinergic properties can 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 CYP1A1/2, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 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 CYP3A4. Co-administration of ketoconazole (200 mg per day), a strong CYP3A4 inhibitor, caused a twofold increase in the AUC of solifenacin, and at a dose of 400 mg per day, a threefold increase. Therefore, the maximum dose of Vesicare should not exceed 5 mg if the patient is concomitantly 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. Since solifenacin is metabolized by CYP3A4, pharmacokinetic interactions with other CYP3A4 substrates with higher affinity (verapamil, diltiazem) and with CYP3A4 inducers (rifampicin, phenytoin, carbamazepine) are possible. Effect of solifenacin on the pharmacokinetics of other drugs Oral contraceptives: no pharmacokinetic interaction of solifenacin and combined oral contraceptives (ethinyl estradiol/levonorgestrel) has been identified. Warfarin: Vesicare® administration did not cause changes in the pharmacokinetics of R-warfarin or S-warfarin or their effect on PT. Digoxin: Vesicare® had no effect on the pharmacokinetics of digoxin. Orally, with liquid, regardless of the time of meal, 5 mg 1 time per day. If necessary, the dose can be increased to 10 mg 1 time per day. The highest dose of solifenacin used by volunteers was 100 mg as a single dose. The most commonly reported side effects at this dose were headache (mild), dry mouth (moderate), dizziness (moderate), drowsiness (mild), and blurred vision (moderate). No cases of acute overdose have been reported. Treatment: administration of activated carbon, gastric lavage; vomiting should not be induced. As in cases of overdose of other anticholinergic drugs, symptoms should be treated as follows: - for severe central anticholinergic effects (hallucinations, severe excitability) - physostigmine or carbachol; - for convulsions or severe excitability - benzodiazepines; - in case of respiratory failure - artificial respiration; - for tachycardia - beta-blockers; - in case of urinary retention - catheterization; - for mydriasis - instill pilocarpine into the eyes and/or darken the room where the patient is. 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 cardiac disease (myocardial ischemia, arrhythmia , congestive heart failure). hypersensitivity to the components of the drug; urinary retention; severe gastrointestinal diseases (including toxic megacolon); myasthenia gravis; angle-closure glaucoma; hemodialysis; severe liver failure; severe renal failure or moderate liver failure during concomitant treatment with strong CYP3A4 inhibitors, such as ketoconazole.
Possible product names
- Vesicare tablet p.p.o. 5mg No. 30
- VESICAR 5 MG TAB. P/OB. No. 30
- VESICAR 0.005 N30 TABLE P/PLEN/COAT
- VESICAR TABLE. P/O PLEN 5 MG X30
- VESICAR TAB. P/O PLEEN. 5 MG No. 30
- VESICAR 5MG TAB. P/PL/OB. X30 (SECONDARY PACKAGE PRINTED)
- (Vesicare) Vesicare tablet. p.p.o. 5mg No. 30
- VESICAR 5 MG TAB. P/OB. No. 30
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 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.
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
ZdravCity
- Vesicare tablets p.p.o.
5mg 30 pcs.Astellas Pharma Europe BV RUB 707 order - Vesicare tablets p.p.o. 10 mg 30 pcs. Astellas Pharma Europe B.V.
RUR 978 order
Pharmacy Dialogue
- Vesicare (tab.pl/vol.5mg No. 30)Astellas Pharma
RUR 764 order
- Vesicare (tab.pl/vol. 10 mg No. 30)Astellas Pharma
RUB 1,094 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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