Pharmacological properties Vesicare 5 mg:
Vesicare in vitro studies and in vivo studies revealed that Solifenacin is a competitive specific antagonist of cholinergic receptors primarily M3 subtype. Solifenacin has a low affinity for other receptors and ion channels.
The therapeutic effect of the drug, which was studied in several double-blind, randomized, controlled clinical trials in men and women with overactive bladder syndrome, observed already in the 1st week of treatment and stabilized during the following 12 weeks of treatment. The maximum effect of the drug can be observed already after 4 weeks. The efficacy of long-term use remains.
After oral administration, maximum concentration of solifenacin plasma levels achieved in 3-8 hours time to reach maximum plasma concentration is independent of dose. The maximum concentration and AUC increased in proportion to dose in the range 5-40 mg. The absolute bioavailability of approximately 90%. Food intake has no effect on the maximum concentration and AUC. Volume of distribution of solifenacin after i / v administration of approximately 600 liters. Solifenacin is largely (about 98%) is bound to plasma proteins, mainly α1-acid glycoprotein.
Solifenacin is actively metabolized in the liver, primarily by cytochrome P450 3A4 (CYP 3A4). Systemic clearance of solifenacin is approximately 9.5 l / h, the final period of its half-life 45-68 hours after oral administration of the drug in blood plasma, except for solifenacin were identified by a pharmacologically active (4R-gidroksisolifenatsin) and three inactive metabolites (N-glucuronide , N-oxide and 4R-hydroxy-N-oxide solifenacin).
After a single injection of 10 mg of 14C-labeled solifenacin 26 days approximately 70% of the radiolabel determined in urine and 23% – in the feces. In the urine as unchanged active substance derived approximately 11% of the radiolabel, approximately 18% – in the form of N-oxide metabolite, 9% – metabolite 4R-hydroxy-N-oxide and 8% – 4R-hydroxy metabolite (active metabolite).
In the range of therapeutic doses of linear pharmacokinetics.
There is no need to adjust the dose depending on age. It is established that exposure to solifenacin (when taken in doses of 5 and 10 mg), expressed as AUC, was similar in healthy elderly (65-80 years) and in young and mature (younger than 55 years). The average rate of absorption, expressed as a time to reach peak concentration was slightly lower and the terminal half-life of approximately 20% longer in the elderly. These minor differences are not clinically significant. The pharmacokinetics of solifenacin does not depend on the patient’s sex and race.
AUC and maximum concentration of solifenacin in patients with mild to moderate renal insufficiency significantly different from those in healthy subjects. In patients with severe renal impairment (creatinine clearance
INDICATIONS Vesicare 5 mg:
The Urge (mandatory), urinary incontinence, frequent urination and Urgent (imperative) urination characteristic of patients with overactive bladder syndrome.
Application: The recommended dose for adults – 5 1 mg once daily with or without food, drinking the liquid. If necessary, the dose may be increased to 10 mg 1 time per day.
CONTRAINDICATIONS Vesicare 5 mg:
Hypersensitivity to solifenacin, or other components of the drug, urinary retention, severe gastrointestinal diseases (including toxic megacolon), myasthenia gravis, angle-closure glaucoma, hemodialysis, severe hepatic, severe renal or hepatic failure of moderate severity and treatment, while a potent inhibitor of cytochrome CYP 3A4 (eg ketoconazole).
SIDE EFFECTS Vesicare 5 mg:
The use of Vesicare possible side effects associated with anticholinergic action solifenacin, which are usually weakly or moderately expressed and dose-related. The most frequent side effects – dry mouth. Dry mouth, usually mild, and only in rare cases requires the removal of the drug.
The incidence of adverse events classified as follows: very common (
Gastrointestinal: Frequent – nausea, indigestion, constipation, abdominal pain, infrequent – dryness of the pharynx, gastro-oesophageal reflux, rarely, in rare cases – obstruction of the colon, coprostasia.
CNS: rare – drowsiness, impaired taste.
From the senses: common – blurred vision (disturbance of accommodation), Uncommon: dry eyes.
Infections and infestations: not often – urinary tract infection.
General disorders: rarely – fatigue, lower extremity edema.
The respiratory system: Infrequent – dryness of nasal mucosa.
For the skin: Infrequent – dry skin.
From the urinary system: Infrequent – difficulty urinating, in rare cases – urinary retention.
PRECAUTIONS Vesicare 5 mg:
Before the start of drug treatment is necessary to establish the likelihood of other causes of frequent urination (kidney disease, heart failure or other). If you found a urinary tract infection, you should start appropriate antibiotic therapy.
The drug should be used with caution in patients with clinically significant obstruction of the opening of the bladder, obstructive diseases of the digestive tract, gastrointestinal motility disorders, severe renal (creatinine clearance
It should not be prescribed the drug to patients with congenital disorders of sensitivity to galactose, lactase deficiency or glucose-galactose malabsorption.
The effect of the drug already noted in the 1st week of treatment, but the maximum effect is achieved after 4 weeks of therapy.
Data on the use of the drug have no children.
Because of its ability, like other anticholinergics may cause a decrease in the rate of accommodation and psychomotor reactions, the question of the appropriateness of potentially hazardous activities need to be addressed only after evaluating the individual patient’s response to the drug.
No clinical data on the use of solifenacin in pregnancy, but in experimental studies revealed no direct adverse effects on fertility, fetal development or during childbirth. Therefore caution should be exercised when using the drug in pregnant women.
No data on the excretion of solifenacin in breast milk, so use Vesicare during breast-feeding is not recommended.
INTERACTION Vesicare 5 mg:
concomitant use of other drugs with anticholinergic properties may have a more pronounced therapeutic effect, and to show more side effects. After stopping Vezikara to use other means to the anticholinergic effect should be kept approximately 1 week interval.
The therapeutic effect of solifenacin may be reduced by simultaneous administration of cholinergic receptor agonists. Solifenacin can reduce the effectiveness of stimulants motility gastrointestinal tract (metoclopramide, cisapride).
While receiving ketoconazole or other potent inhibitor of the enzyme CYP 3A4 (eg ritonavir, nelfinavir, itraconazole) Vesicare dose should be reduced to 5 mg. Simultaneous administration of solifenacin and the active enzyme CYP 3A4 inhibitor is contraindicated in patients with severe renal or moderate hepatic impairment.
Since Solifenacin is metabolised by the enzyme CYP 3A4, are possible pharmacokinetic interactions with other substrates of this enzyme (such as verapamil, diltiazem) and inducers of the enzyme CYP 3A4 (eg rifampicin, phenytoin, carbamazepine).
There was no pharmacokinetic interaction between solifenacin with combined oral contraceptives (ethinyl estradiol / levonorgestrel).
Vesicare not affect the pharmacokinetics of warfarin and digoxin.
Overdose Vesicare 5 mg:
The maximum dose used was 100 mg of the drug dose. It was noted side effects such as slight headache, moderate dry mouth, dizziness, drowsiness, blurred vision.
In case of overdose should be gastric lavage and activated charcoal to appoint. As with other anticholinergic drugs overdose, conduct the following activities: when expressed central effects (hallucinations, agitation) – physostigmine or carbachol, with cramps – benzodiazepines, with respiratory failure – mechanical ventilation, with urinary retention – catheterization of the bladder, with mydriasis – burial in pilocarpine eye or placing the patient in a darkened room, with tachycardia – β-adrenoceptor blockers. Particular attention should be given to patients at risk lengthening the Q-T interval on the ECG (with hypokalemia, bradycardia, concomitant use of drugs known to cause prolongation of the interval Q-T) and patients with heart disease (IHD, arrhythmia, congestive heart failure).
