Vesicar

Vesicare is used in urological practice. It is a medicine for the treatment of incontinence and rapid urination.

Indications of the vesicara

It is used in the process of symptomatic therapy of urinary incontinence or frequent urination, and in addition to eliminating the urgent urge to empty the urea, which are often found in people with GMF disease.

Release form

The release takes place in tablets, 10 pieces inside a blister pack. Inside a single pack of drugs - 1 or 3 blister plates.

Pharmacodynamics

Solifenacin is an antagonist of acetylcholine receptors of a competitive type with a specific effect. The ureter is innervated by parasympathetic acetylcholine nerve endings. The substance acetylcholine helps to reduce the smooth muscle detrusora, in addition to affecting the muscarinic ends, which are mainly included in the subtype MZ.

Tests in vitro, and with it in vivo, have shown that the substance solifenacin mainly affects exactly the endings that have the MZ subtype. In addition, it was found that the substance has a weak affinity or its complete absence with other endings, as well as the test channels of ions.

The effect of the drug was studied with several double-type blind tests that were clinically monitored and conducted on women and men with GMF. The effect was manifested already during the first treatment week and stabilized during the following 12 weeks of the course. In open tests with a longer duration of application, it was found that Vesicare exposure can be maintained for a minimum of 12 months.

[1], [2], [3]

Pharmacokinetics

After oral administration of drugs, the peak plasma index is observed after 3-8 hours. The period of time spent on reaching the peak level does not depend on the size of the dosage. The peak value and AUC value increase in accordance with the dosage in the range of 5-40 mg. The bioavailability level is approximately 90%. The consumption of food does not affect the values of AUC and the peak concentration of the substance.

Virtually all solifenacin (about 98%) is synthesized with a plasma protein - mainly with an α1-acid glycoprotein.

Most of the substance passes the metabolism inside the liver, mainly with the help of hemoprotein P450-ZA4 (element CYP3A4). The indicator of the system clearance of the component is approximately 9.5 l / h, and the terminal half-life time is 45-68 hours. In the internal application of drugs, 1 pharmacoactive decay product (element 4R-hydroxy-salifenacin), as well as 3 more inactive (elements of N-glucuronide with N-oxide, as well as 4R-hydroxy-N-oxide of solifenacin substance) are found inside the plasma inside the plasma.

With a one-time intake of 10 mg of medication (14C-tagged), about 70% of the radioactive substance is found inside the urine, and another 23% inside the feces. About 11% of the radioactive element inside urine is excreted in the form of an unchanged active substance. Another 18% is in the form of the N-oxide decomposition product, and 9% is disguised as the decay product of 4R-hydroxy-N-oxide, and at the same time, 8% is disintegrated as the active product of 4R-hydroxymetabolite decomposition.

In the intervals between the use of medicinal dosages of a drug, its pharmacokinetics remains linear.

[4], [5]

Dosing and administration

The standard adult dosage for a day is a single dose of 5 mg of Vesicare. If necessary, it is allowed to increase it to a single dose of 10 mg per day.

People with kidney failure in severe degree (at a level of QC ≤30 ml / minute) are required to use drugs with caution - for a day to take a maximum of 5 mg.

Persons with liver failure in moderate form (level 7-9 Child-Pugh) also need to consume not more than 5 mg of medication per day.

If used together with powerful drugs-inhibitors of hemoprotein P450 3A4 (among these ketoconazole, and other powerful inhibitors of the isoform of the hemoprotein CYP3A4 - itraconazole with nelfinavir and ritonavir), the maximum dosage size of the drug should be 5 mg.

Vesicare is used orally. Tablets should be swallowed whole, washed down with water. The reception is not dependent on eating.

[9], [10], [11], [12], [13]

Use of the vesicara during pregnancy

Information about women who became pregnant during the use of solifenacin, no. Animal tests showed no direct adverse effect on fertility, as well as fetal development and the delivery process. There is no information about the potential risk of violations. It is required with care to prescribe Vesicare pregnant.

There is no information about the ingestion of the substance into the mother's milk. The active component and its decay products when tested in mice passed into milk and provoked a dose-dependent insufficiency of growth in the born mice. As a consequence, use of the drug in lactation is prohibited.

Contraindications

Among the main contraindications:

• the presence of increased sensitivity with respect to the active component of the drug or other of its additional elements;
• persons with a delay in the process of urination, and in addition with severe pathology of the gastrointestinal tract (this includes a megacolon of toxic type), myasthenia gravis or glaucoma of the closed type, as well as people with a tendency to develop such diseases;
• the period of completion of hemodialysis procedures;
• liver failure in severe degree;
• Persons with liver failure in moderate form or kidneys in severe form treated with inhibitors of the hemoprotein CYP3A4 - for example, ketoconazole.

No tests were conducted regarding the efficacy and safety of taking Vesicare by children, so it is not recommended to prescribe this group of patients.

[6]

Side effects of the vesicara

The use of drugs can cause such side effects:

• invasive and infectious pathologies: sometimes develops cystitis or infection in the area of the organs of urination;
• immune reactions: anaphylactic manifestations may occur;
• disorders of the digestive function and metabolic processes: there may be hyperkalemia or impaired appetite;
• mental illness: single appear hallucinations, as well as a sense of confusion. Delirium can develop;
• reactions of the NS: sometimes develop disorders of taste buds, as well as a feeling of drowsiness. Occasionally there are dizziness or headaches;
• violations in the work of visual organs: often there is visual fuzziness. Sometimes the dryness of the eye mucous can develop. There may be a glaucoma;
• disorders in the work of the heart: the development of pirouette tachycardia, atrial fibrillation, tachycardia or palpitation, and prolongation of the QT interval on the ECG;
• manifestations of the respiratory system and mediastinum with the sternum: sometimes the dryness of the nasal mucosa develops. Dysphonia appears;
• reactions of the digestive tract: most often there is dryness of the oral mucosa. Also often there is nausea, constipation, and in addition there are abdominal pains and dyspepsia. Sometimes there is dryness in the throat and GERD. Occasionally, vomiting, fecal obstruction, and obstruction inside the large intestine develop. There may be discomfort in the abdomen and intestinal obstruction;
• Dysfunction of the hepatobiliary system: possibly functional hepatic disorder and changes in laboratory tests of liver samples;
• subcutaneous layer and skin: dry skin is sometimes observed. Occasionally there is a rash or itching. There is a hives, polyformiform erythema or angioedema. Possible development of exfoliative form of dermatitis;
• disturbances in the work of ODA and connective tissues: weakness in muscles may appear;
• disorders in the system of urination and kidneys: sometimes there are problems with urination. Occasionally there is a delay in the process of urination. Possible development of kidney failure;
• systemic disorders: sometimes there is increased fatigue and swelling of the peripheral type.

[7], [8],

Overdose

A substance overdose suifinate solifenacin succinate can cause severe cholinolytic effects. The highest dosage of the component, used by one patient unintentionally, was equal to 280 mg in a period of 5 hours. At the same time, changes in his mental state developed, but he did not need hospitalization.

When the medicine is intoxicated, it is required to use activated charcoal. The gastric lavage procedure may be useful (provided it is performed at least 1 hour after taking the drug), but it is not recommended to induce vomiting.

Concerning other holinolitic manifestations, their signs can be eliminated in such ways:

• with severe form of disorders in the central nervous system (for example, with increased excitability or hallucinations), it is required to use the drug Carbachol, as well as physostigmine;
• with strong excitability or bouts of seizures, benzodiazepines are used;
• when respiratory failure occurs, an artificial respiration procedure is required;
• when developing tachycardia, β-blockers are used;
• when the urinary process is delayed, a catheterization is prescribed;
• In the case of mydriasis, eye drops are used, such as pilocarpine. Moving the victim into a dark room can also help.

As in the case of poisoning with other holinolitic drugs, it is especially necessary to watch people who have been diagnosed with the risk of prolonging the QT interval (in the case of bradycardia or hypokalemia, and also when combining the drug with agents provoking prolongation), as well as for people with cardiac pathologies (such as arrhythmia, heart failure and myocardial ischemia).

[14], [15]

Interactions with other drugs

Due to the combined use with other anticholinergic drugs, it is possible to develop pronounced drug reactions, as well as side effects. After discontinuation of Vesicare use, it  is required to maintain an interval (about 1 week) before using the following drugs for cholinolytic treatment.

The therapeutic effect of solifenacin can be weakened in the case of combination with agonists of acetylcholine terminals. The substance may impair the properties of drugs that stimulate the peristalsis of the gastrointestinal tract (eg, cisapride or metoclopramide).

Metabolism solifenacin is carried out with the help of the enzyme CYP3A4. When combined with ketoconazole (intake of 200 mg per day), which is a potent inhibitor of the element CYP3A4, an increase in the AUC level of the substance is doubled. When combined with ketoconazole in a daily dose of 400 mg, this figure is tripled. Consequently, the size of the maximum dosage of drugs in the case of a combination with ketoconazole and drug doses of other strong inhibitors of the CYP3A4 enzyme is limited to 5 mg.

The combination of Vesicare with powerful inhibitors of the enzyme CYP3A4 is prohibited for persons with liver failure (moderate degree) or kidney (severe).

There is no information on studies of the effect of induction enzymes on the pharmacokinetics of solifenacin with its degradation products, and in addition on the activity of substrates having the enhanced affinity of the element CYP3A4 and its decay products with the exposure index of the solifenacin component.

Because the metabolism of solifenacin is carried out with the help of the enzyme CYP3A4, drug interactions with other substrates of this enzyme with increased affinity (among them diltiazem with verapamil), and in addition with inducers of the enzyme CYP3A4 (among them phenytoin with rifampicin and carbamazepine) can be observed.

[16], [17], [18], [19], [20],

Storage conditions

Vesicare must be kept in a place that will not be accessible to young children. The temperature level is not more than 25 ° С.

[21], [22], [23]

Shelf life

Vesicare is allowed to be used in the period of 3 years from the date of manufacture of the medicine.