Vesicare® [Solifenacin]

Brand Astellas

In stock 1100 Items

Available since: 2019-09-19

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Clinical Pharmacology

Farm group: antispasmodic.
Pharmacological action: Pharmacological studies carried out in vitro and in vivo have shown that solifenacin is a specific competitive inhibitor of muscarinic receptors, predominantly of the M3 subtype. It was also found that solifenacin has low or no affinity for various other receptors and ion channels. ?
The efficacy 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 during the first week of treatment and stabilized over the next 12 weeks of treatment.
The maximum Vesicare effect can be detected after 4 weeks. Effectiveness persists for prolonged use (at least 12 months).
Pharmacokinetics: General Characteristics
Absorption: The maximum plasma concentration (Cmax) is reached after 3-8 hours. The time to reach the maximum concentration (tmax) does not depend on the dose. Сmax and area under the curve (AUC) concentration dependences on time increase in proportion to the dose increase from 5 to 40 mg. Absolute bioavailability - 90%. Eating does not affect the Cmax and CPD of solifenacin.
Distribution: The volume of distribution of solifenacin after intravenous administration is approximately 600 liters. Solifenacin is largely (about 98%) associated with plasma proteins, mainly with the α1-acid glycoprotein.
Metabolism: Solifenacin is actively metabolized by the liver, mainly cytochrome P450 ZA4 (CYP3A4). However, there are alternative metabolic pathways through which solifenacin may be metabolized. Systemic clearance of solifenacin is about 9.5 l / h, and the final half-life is 45-68 hours. After taking the drug inside the 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 solifenacin).
Withdrawal: After a single injection of 10 mg of 14C-labeled solifenacin after 26 days, about 70% of the radioactivity was detected in the urine and 23% in the feces. In the urine, about 11% of the radioactivity was detected as unchanged active substance, about 18% as N-oxide metabolite, 9% as 4R-hydroxy-N-oxide metabolite, and 8% as 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 the patients. Studies have shown that exposure to solifenacin (5 and 10 mg), expressed as CPD, was similar in healthy elderly individuals (65 to 80 years old) and in healthy young individuals (<55 years="" old="" the="" average="" absorption="" rate="" expressed="" as="" tmax="" was="" slightly="" lower="" and="" final="" half-life="" is="" about="" 20="" longer="" in="" elderly="" these="" minor="" differences="" are="" not="" clinically="" significant="" pharmacokinetics="" of="" solifenacin="" have="" been="" determined="" children="" adolescents="" gender:="" independent="" gender="" patient="" race:="" race="" does="" affect="" renal="" failure:="" auc="" cmax="" patients="" with="" mild="" to="" moderate="" insufficiency="" different="" from="" those="" healthy="" volunteers="" severe="" creatinine="" clearance:="" hepatic="" insufficiency:="" impairment="" child-pugh="" indicator="" 7="" 9="" change="" pep="" increases="" by="" 60="" t1="" 2="" doubles="" failure="" p="">

Indications

Treatment of urgent (imperative) urinary incontinence, frequent urination and urgent urging characteristic of patients with overactive bladder syndrome.

Composition

1 tab .:
- solifenacin succinate 10 mg
Excipients: lactose monohydrate - 102.5 mg, corn starch - 30 mg, hypromellose 3 MPa × s - 6 mg, magnesium stearate - 1.5 mg.
The composition of the film shell: opadry pink 03F14895 (hypromellose 6 MPa × with 62%, talc 18.59%, macrogol 8000 11.63%, titanium dioxide 7.75%, iron red oxide 0.03%) - 4 mg

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Dosage and Administration

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

Adverse reactions

Vesicare may cause side effects associated with the anticholinergic action of solifenacin, usually with mild or moderate severity. The frequency of these adverse effects is dose dependent. The most common 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 a placebo. The severity of dry mouth was usually mild and only rarely led to interruption of treatment. Overall, compliance (compliance) was very high.

The table below summarizes the other side effects recorded in Vesicare clinical studies:

Side effects	Often (≥1 / 100, Infrequently (≥1 / 1000, Rarely (≥1/10000,
Gastrointestinal disorders	constipation, nausea, dyspepsia, abdominal pain	gastroesophageal reflux disease, dry pharynx	colonic obstruction, coprostasis
Infections and invasions		urinary tract infection
Nervous system disorders		drowsiness, dysgeusia (taste disturbance)
Violations of the organs of sight	blurred vision (disturbed accommodation)	dry eyes
General Disorders		fatigue, swelling of the lower limbs
Disorders of the respiratory system, chest and mediastinum		dry nasal cavity
Violations of the skin and subcutaneous tissue		dry skin
Kidney and urinary tract disorders		difficulty urinating	urinary retention

Allergic reactions were not observed during clinical trials. However, the possibility of allergic reactions should not be excluded.

Contraindications

Hypersensitivity to the components of Vesicare;
urinary retention;
severe gastrointestinal diseases (including toxic megacolon);
myasthenia gravis gravis;
angle-closure glaucoma;
hemodialysis;
severe liver failure;
severe renal impairment or moderate hepatic impairment with simultaneous treatment with strong CYP3A4 inhibitors, such as ketoconazole.

Drug interactions

Pharmacological interaction

Concomitant treatment of drugs with anticholinergic properties may lead to more pronounced therapeutic and undesirable effects. After discontinuation of solifenacin, an approximately one week break should be taken before starting treatment with another anticholinergic drug. The therapeutic effect can be reduced while taking cholinergic receptor agonists. Solifenacin can reduce the effect of drugs that stimulate gastrointestinal motility, such as metoclopramide and cisapride.

Pharmacokinetic interaction

Research in vitro showed 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 change the clearance of drugs metabolized by these CYP enzymes.

The effects of other drugs on the pharmacokinetics of solifenacin

Solifenacin is metabolized by CYP3A4. The simultaneous administration of ketoconazole (200 mg per day), a strong inhibitor of CYP3A4, 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 simultaneously takes ketoconazole or therapeutic doses of other strong inhibitors of CYP3A4 (such as ritonavir, nelfinavir, itraconazole). Simultaneous treatment with solifenacin and a strong CYP3A4 inhibitor is contraindicated in patients with severe renal insufficiency or with moderate hepatic insufficiency.Since solifenacin is metabolized by CYP3A4, pharmacokinetic interaction with other CYP3A4 substrates with higher affinity (verapamil, diltiazem) and with CYP3A4 inducers (rifampicin, phenytoin, carbamazepine) is possible.

The effect of solifenacin on the pharmacokinetics of other drugs

Oral contraceptives: no pharmacokinetic interaction of solifenacin and combined oral contraceptives (ethinyl estradiol / levonorgestrel) was detected.

Warfarin: Vesicare did not cause changes in the pharmacokinetics of R-warfarin or S-warfarin, or their effect on PV.

Digoxin: Vesicaret had no effect on digoxin pharmacokinetics.

Pregnancy and Lactation

There is no clinical data on women who become pregnant while taking solifenacin. Animal studies have not revealed a direct adverse effect on fertility, embryo / fetus development, or childbirth. Care should be taken when prescribing this drug to pregnant women.

There are no data on the excretion of solifenacin with milk in humans. The use of Vesicare is not recommended during breastfeeding.

Special instructions

Before starting treatment with Vesicare, it should be ascertained whether there are any other causes of increased urination (heart failure or kidney disease). If urinary tract infection is detected, appropriate antibacterial treatment should be initiated. Vesicare should be carefully prescribed to patients:

- with a clinically significant obstruction of the bladder outlet leading to the risk of urinary retention;

- with gastrointestinal obstructive diseases;

- c risk of reduced GI motility;

- with severe renal (Cl creatinine ≤30 ml / min) and moderate hepatic (Child-Pugh index from 7 to 9) insufficiency; doses for these patients should not exceed 5 mg;

- at the same time taking a strong inhibitor of CYP3A4, for example ketoconazole;

- with hernia of the esophageal orifice of the diaphragm, gastroesophageal reflux, and patients who are simultaneously taking medications (such as bisphosphonates) that can cause or strengthen esophagitis;

- with autonomic neuropathy.

Patients with rare hereditary disorders of the tolerance of galactose, lactase deficiency of lapps (Saami), glucose-galactose malabsorption should not take the drug.

Solifenacin, like other anticholinergic drugs, can cause blurred vision, and (rarely) drowsiness and fatigue, which can adversely affect your ability to drive and work with machinery.

Overdosage

The highest dose of solifenacin, which was used by volunteers, was 100 mg in a single dose. At this dose, the following side effects were most often noted: headache (mild), dry mouth (moderate), dizziness (moderate), drowsiness (mild) and blurred vision (moderate). No cases of acute overdose have been reported.

Treatment: the appointment of Activated charcoal, gastric lavage; vomiting should not be caused.

As in cases of overdose of other anticholinergics, the symptoms should be treated as follows:

- with severe central anticholinergic effects (hallucinations, marked excitability) - physostigmine or carbachol;

- for convulsions or marked irritability - benzodiazepines;

- for respiratory failure - artificial respiration;

- with tachycardias - beta-blockers;

- with urinary retention - catheterization;

- in case of mydriasis - instillation of pilocarpine into the eyes and / or darkening of the room where the patient is located.

As in the case of overdose of other anticholinergic drugs, special attention should be paid to patients with an established risk of prolonging the QT interval (i.e.with hypokalemia, bradycardia and while taking drugs that cause prolongation of the QT interval and patients with heart disease (myocardial ischemia, arrhythmia, congestive heart failure).