Vesicar

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

Indications Vezikara

It is used in the process of symptomatic therapy of urgent incontinence or frequent urination, and in addition to this, to eliminate the urgent urge to empty the bladder, which often occurs in people with OAB disease.

Release form

The release occurs in tablets, 10 pieces inside a blister pack. Inside a separate pack of medicine - 1 or 3 blister plates.

Pharmacodynamics

Solifenacin is a competitive acetylcholine receptor antagonist with specific action. The ureter is innervated by parasympathetic acetylcholine nerve endings. The substance acetylcholine promotes contraction of the smooth muscles of the detrusor, in addition to this, it affects muscarinic endings, which are mainly included in the M3 subtype.

In vitro and in vivo tests have shown that the substance solifenacin mainly affects the endings of the M3 subtype. In addition, it was found that the substance has a weak affinity or no affinity at all with other endings, as well as the ion channels tested.

The drug's effects were studied in several double-blind clinically controlled trials in women and men with OAB. The effect was evident as early as the first week of treatment and stabilized over the next 12 weeks of treatment. In open trials with longer-term use, it was found that the effects of Vesicare could be maintained for at least 12 months.

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Pharmacokinetics

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

Almost all solifenacin (about 98%) is synthesized with plasma protein, mainly with α1-acid glycoprotein.

Most of the substance undergoes metabolism in the liver, mainly with the help of hemoprotein P450 ZA4 (element CYP3A4). The systemic clearance rate of the component is approximately 9.5 l/hour, and its terminal half-life reaches 45-68 hours. When the drug is administered internally, in addition to the active component, 1 pharmacoactive decay product (element 4R-hydroxysolifenacin) is detected in the plasma, as well as 3 more inactive ones (elements N-glucuronide with N-oxide, as well as 4R-hydroxy-N-oxide of the substance solifenacin).

With a single dose of 10 mg of the drug (14C-labeled), about 70% of the radioactive substance is found in the urine, and another 23% in the feces. About 11% of the radioactive element in the urine is excreted in the form of unchanged active substance. Another approximately 18% is excreted in the form of the N-oxide decay product, and 9% as the 4R-hydroxy-N-oxide decay product, and together with this, 8% is excreted as the active decay product 4R-hydroxy metabolite.

During the intervals between doses of the drug, its pharmacokinetics remain linear.

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Dosing and administration

The standard adult dosage per day is a single dose of 5 mg of Vesicare. If necessary, it can be increased to a single dose of 10 mg per day.

People with severe renal insufficiency (with a CC level ≤30 ml/minute) should use the drug with caution - take a maximum of 5 mg per day.

People with moderate liver failure (Child-Pugh score 7-9) should also take no more than 5 mg of the drug per day.

In case of use together with potent drugs-inhibitors of hemoprotein P450 3A4 (among them ketoconazole, as well as other potent inhibitors of the isoform of hemoprotein CYP3A4 – itraconazole with nelfinavir and ritonavir), the maximum dosage of the drug should be 5 mg.

Vesicare is taken orally. The tablets should be swallowed whole with water. It is not dependent on food intake.

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Use Vezikara during pregnancy

There is no information on women becoming pregnant while using solifenacin. Animal tests have not shown any direct negative effects on fertility, fetal development or the birth process. There is no information on the potential risk of disorders. Vesicare should be used with caution in pregnant women.

There is no information regarding the penetration of the substance into mother's milk. The active component and its breakdown products passed into milk during tests on mice and provoked dose-dependent growth failure in newborn mice. As a result, the use of the drug during lactation is prohibited.

Contraindications

Among the main contraindications:

• the presence of increased sensitivity to the active component of the drug or its other additional elements;
• people with urinary retention, as well as with severe gastrointestinal pathologies (this includes toxic megacolon), myasthenia gravis or closed-angle glaucoma, as well as people with a tendency to develop such diseases;
• period of hemodialysis procedures;
• severe liver failure;
• persons with moderate liver failure or severe renal failure treated with CYP3A4 hepatic inhibitors, such as ketoconazole.

No tests have been conducted on the efficacy and safety of Vesicare in children, so it is not recommended for use in this group of patients.

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Side effects Vezikara

The use of drugs may cause the following side effects:

• invasive and infectious pathologies: sometimes cystitis or infections in the urinary tract develop;
• immune reactions: anaphylactic reactions may occur;
• disorders of digestive function and metabolic processes: hyperkalemia or loss of appetite may occur;
• mental illness: hallucinations appear sporadically, and a feeling of confusion arises. Delirium may develop;
• NS reactions: sometimes taste bud disorders develop, as well as a feeling of drowsiness. Occasionally, dizziness or headaches occur;
• visual impairment: visual blurring often occurs. Dryness of the mucous membranes of the eye may sometimes develop. Glaucoma may develop;
• disorders in the functioning of the heart: development of torsades de pointes, atrial fibrillation, tachycardia or palpitations, as well as prolongation of the QT interval on the ECG;
• manifestations of the respiratory system and mediastinum with the sternum: sometimes dryness of the nasal mucosa develops. Dysphonia may occur;
• reactions of the gastrointestinal tract: most often, dryness of the oral mucosa is observed. Nausea, constipation, abdominal pain and dyspeptic symptoms also often occur. Sometimes, dryness in the throat and GERD occur. Vomiting, fecal impaction, and obstruction inside the colon occasionally develop. Discomfort in the abdominal area and intestinal obstruction may occur;
• dysfunction of the hepatobiliary system: possible functional liver disorder and changes in laboratory test results of liver samples;
• subcutaneous layer and skin: sometimes dry skin is observed. Rarely, a rash or itching appears. Urticaria, erythema multiforme or angioedema occur occasionally. Exfoliative dermatitis may develop;
• disorders in the functioning of the musculoskeletal system and connective tissues: muscle weakness may appear;
• urinary and renal disorders: sometimes there are problems with urination. Occasionally, there is a delay in the process of urination. Kidney failure may develop;
• systemic disorders: sometimes there is increased fatigue and peripheral edema.

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Overdose

Overdose of the substance succinate solifenacin succinate can cause severe anticholinergic effects. The highest dose of the component, taken by one patient unintentionally, was 280 mg over a period of 5 hours. At the same time, changes in his mental state developed, but he did not need hospitalization.

In case of drug intoxication, activated carbon should be taken. Gastric lavage may be helpful (provided it is performed at least 1 hour after taking the drug), but inducing vomiting is not recommended.

As for other anticholinergic manifestations, their symptoms can be eliminated in the following ways:

• in severe cases of CNS disorders (for example, increased excitability or hallucinations), it is necessary to use the drug Carbachol, as well as physostigmine;
• In case of severe excitability or seizures, benzodiazepines are used;
• if respiratory failure occurs, artificial respiration must be performed;
• if tachycardia develops, β-blockers are used;
• if there is a delay in urination, catheterization is prescribed;
• In case of mydriasis, eye drops such as pilocarpine are used. Moving the victim to a dark room may also help.

As with poisoning with other anticholinergic drugs, it is especially important to carefully monitor individuals who have been diagnosed with a risk of prolongation of the QT interval (in the case of bradycardia or hypokalemia, and also when combining the drug with agents that provoke prolongation), as well as people with cardiac pathologies (such as arrhythmia, heart failure and myocardial ischemia).

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Interactions with other drugs

Due to the combined use with other anticholinergic drugs, the development of severe drug reactions and side effects is possible. After stopping the use of Vesicare, it is necessary to wait a period (about 1 week) before using the following drugs for anticholinergic treatment.

The medicinal effect of solifenacin may be weakened when combined with acetylcholine ending agonists. The substance may weaken the properties of drugs that stimulate gastrointestinal motility (for example, cisapride or metoclopramide).

Solifenacin is metabolized by the CYP3A4 enzyme. When combined with ketoconazole (200 mg daily), which is a potent inhibitor of the CYP3A4 element, the AUC level of the substance doubles. When combined with ketoconazole at a daily dose of 400 mg, this indicator triples. As a result, the maximum dosage of the drug in the case of a combination with ketoconazole and medicinal doses of other strong inhibitors of the CYP3A4 enzyme is limited to 5 mg.

The combination of Vesicare with potent CYP3A4 inhibitors is contraindicated in individuals with moderate liver or severe kidney failure.

There are no data on studies of the effect of induction enzymes on the pharmacokinetic parameters of solifenacin with its breakdown products, and in addition to this, on the activity of substrates with increased affinity for the CYP3A4 element and its breakdown products with the exposure parameter of the solifenacin component.

Since solifenacin is metabolized by the CYP3A4 enzyme, drug interactions with other substrates of this enzyme that have increased affinity (including diltiazem with verapamil) and also with inducers of the CYP3A4 enzyme (including phenytoin with rifampicin and carbamazepine) may be observed.

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Storage conditions

Vesicare should be kept in a place inaccessible to small children. The temperature level should not exceed 25°C.

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Shelf life

Vesicare is approved for use for a period of 3 years from the date of manufacture of the medicine.