Vesicare, pills 5mg, 30pcs

Composition

1 coated tablet contains an Active ingredient:

solifenacin succinate 5 mg;

excipients:

lactose monohydrate;

corn starch;

hypromellose 3 MPa * s;

magnesium stearate;

purified water

Pharmacological action

Pharmacodynamics

Pharmacological studies conducted in vitro and in vivo have shown that solifenacin is a specific competitive inhibitor of muscarinic receptors, mainly of the M3 subtype. It was also found that solifenacin has a low affinity or does not interact with other receptors and ion channels.

The efficacy of Vesicar, which was 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 during the next 12 weeks of treatment. The maximum effect of Vesicar can be detected after 4 weeks. The effectiveness is maintained during long-term use (at least 12 months).

Pharmacokinetics

General Features

Absorption. Cmax is reached in 3-8 hours. The time to reach Cmax does not depend on the dose. Cmax and AUC 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 use is 600 liters. Solifenacin is largely (about 98%) bound to plasma proteins, mainly to α1-acid glycoprotein.

Metabolism. Solifenacin is extensively metabolized by the liver, mainly by cytochrome P4503A4 (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 h. After oral use, the following metabolites were identified in plasma in addition to solifenacin: one pharmacologically active (4R-hydroxysolifenacin) and three inactive (N-glucuronide, N-oxide and 4R-hydroxy-N-oxide of solifenacin).

Output. After a single use of 10 mg of 14C-labeled solifenacin 26 days later, about 70% of radioactivity was detected in the urine and 23% in the faeces. In the urine, approximately 11% of radioactivity was detected as an unchanged Active ingredient, about 18% as an N — oxide metabolite,9% as a 4R-hydroxy — N-oxide metabolite, and 8% as a 4R-hydroxy metabolite (active metabolite).

The pharmacokinetics of solifenacin are linear in 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 patients. Studies have shown that solifenacin exposure (5 and 10 mg), expressed as AUC, was similar in healthy elderly individuals (65 to 80 years) and healthy young individuals (max, was slightly lower, and the final T1 / 2 was approximately 20% longer in older people. These minor differences are not clinically significant.

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

Gender. The pharmacokinetics of solifenacin do not depend on the patient’s gender.

Race. Race does not affect the pharmacokinetics of solifenacin.

Kidney failure. The AUC and Cmax of solifenacin in patients with mild to moderate renal insufficiency slightly differ from the corresponding values in healthy volunteers. In patients with severe renal insufficiency (creatinine clearance < 30 ml/min), solifenacin exposure is significantly higher (an 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 hepatic insufficiency (Child-Pugh score from 7 to 9), the Cmax value does not change, AUC increases by 60%, and T1 / 2 doubles. Pharmacokinetics in patients with severe hepatic insufficiency were not determined.

Indications

Urgent (imperative) urinary incontinence, rapid urination, and urgent (imperative) urge to urinate characteristic of patients with overactive bladder syndrome.

Use during pregnancy and lactation

There are no clinical data on women who became pregnant while taking solifenacin.

Animal studies have shown no direct adverse effects on fertility, embryo/fetus development, or delivery.

Caution should be exercised when prescribing this drug to pregnant women.

There are no data on the excretion of solifenacin in milk in humans.

The use of Vesicar is not recommended during breastfeeding.

Contraindications

• hypersensitivity to the components of Vesicar;
• urinary retention;
• severe gastrointestinal diseases (including toxic megacolon);
• myasthenia gravis;
• angle-closure glaucoma;
• hemodialysis;
• severe hepatic insufficiency;
• severe renal insufficiency or moderate hepatic insufficiency with concomitant treatment with strong CYP3A4 inhibitors, such as ketoconazole.

Side effects

Vesicar may cause side effects associated with the anticholinergic effect of solifenacin, usually mild or moderate in severity. The frequency of these adverse effects depends on the dose. The most frequently 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% of patients receiving placebo. The severity of dry mouth was usually mild and only rarely led to discontinuation of treatment. Overall, treatment compliance was very high.

The table below shows the remaining side effects reported in clinical studies of Vesicar:

Side effectscastly (≥1/100, Infrequently (≥1/1000, Rarely (≥1/10000, Gastrointestinal disorders) Constipation, nausea, dyspepsia, abdominal paingastroesophageal reflux disease, dry pharynx, colonic obstruction, coprostasis Infections and infestations urinary tract infection Nervous system disorders drowsiness, dysgeusia (taste disorder) Visual disturbances: Blurred vision (accommodation disorder)dry eyes General condition disorders fatigue, edema of the lower extremities Respiratory, thoracic and mediastinal disorders dryness of the nasal cavity Skin and subcutaneous tissue disorders dry skin Kidney and urinary tract disorders difficulty urinating urinary retention

No allergic reactions were reported during clinical trials. However, the possibility of allergic reactions should not be excluded.

Interaction

Pharmacological interaction

Concomitant treatment of drugs with anticholinergic properties may lead to more pronounced therapeutic and undesirable effects. After stopping taking solifenacin, you should take a break of approximately one week 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 medications 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, it is unlikely that solifenacin will alter the clearance of drugs metabolized by these CYP enzymes.

Effects of other drugs on the pharmacokinetics of solifenacin

Solifenacin is metabolized by CYP3A4. Concomitant use of ketoconazole (200 mg daily), a strong CYP3A4 inhibitor, caused a twofold increase in the AUC of solifenacin, and a three — fold increase at a dose of 400 mg daily. Therefore, the maximum dose of Vesicar 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 insufficiency or moderate hepatic insufficiency. Since solifenacin is metabolized by CYP3A4, it is possible to interact pharmacokinetically with other CYP3A4 substrates with higher affinity (verapamil, diltiazem) and with CYP3A4 inducers (rifampicin, phenytoin, carbamazepine).

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 Vesicar did not cause changes in the pharmacokinetics of R-warfarin or S-warfarin or their effect on PV.

Digoxin: Taking Vesicar did not affect the pharmacokinetics of digoxin.

How to take it, course of use and dosage

Inside, washed down with liquid, regardless of the time of meal,5 mg 1 time a day.

If necessary, the dose can be increased to 10 mg once a day.

Overdose

The highest dose of solifenacin used by the volunteers was 100 mg as a single dose.The most common side effects reported 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: use of activated charcoal, gastric lavage; vomiting should not be induced.

As with overdoses of other anticholinergic agents, symptoms should be treated as follows::

– in severe Central anticholinergic effects (hallucinations, severe anxiety) — physostigmine or carbachol;

– in convulsions or severe anxiety — benzodiazepines;

– respiratory failure — artificial respiration;

– tachycardia — beta-blockers;

– if urinary retention — catheterization;

– when mydriasis — instillation in the eye of pilocarpine and/or dimming the room where the patient is located.

As with overdoses of other anticholinergic drugs, special attention should be paid to patients who have an established risk of QT prolongation (i. e., hypokalemia, bradycardia, and concomitant use of drugs that cause QT prolongation) and patients with heart disease (myocardial ischemia, arrhythmia, congestive heart failure).

Special instructions

Before starting treatment with Vesicar, you should determine 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 initiated. Vesicar should be administered with caution to patients:

– with clinically significant obstruction of the outlet of the bladder, leading to the risk of urinary retention;

– c gastrointestinal obstructive disease;

the risk of reduced motility of the gastrointestinal tract;

– c severe renal (creatinine Cl ≤30 ml/min) and moderate hepatic (a measure of Child-Pugh 7 to 9) a failure; the dose for these patients should not exceed 5 mg;

– at the same time receiving a strong CYP3A4 inhibitor, e. g. ketoconazole;

– with a hernia hiatal, gastroesophageal reflux and patients concurrently taking drugs (such as bisphosphonates) that can cause or exacerbate esophagitis;

– the Autonomous neuropathy.

Patients with rare hereditary problems of galactose tolerance, lapidary (Sami) lactase deficiency, glucose-galactose malabsorption should not take the drug.

Solifenacin, like other anticholinergic drugs, can cause blurred vision, as well as (rarely) drowsiness and fatigue, which can negatively affect the ability to drive a car and work with mechanisms.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Solifenacin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For pregnant women as prescribed by a doctor, For adults as prescribed by a doctor

Indications

Enuresis