Expiration date: 05/2026
dosage form
Round biconvex film-coated tablet Brownish-red with engraving "6 / 0.4" on one side
Composition
Each tablet contains: active substances - solifenacin succinate 6.0 mg of tamsulosin hydrochloride 0.4 mg,
Excipients - mannitol 83.0 mg, 10.0 mg of maltose, 2.2 mg of magnesium stearate, macrogol 7 000 000 200.0 mg Macrogol 8000 40.0 mg
shell composition - red Opadry 03F45072 (Valium 6 MPa, with 69.536%, iron oxide red dye 17.440%, 13.024% macrogol 8000) 10.2 mg.
Each bilayer tablet contains a single layer of solifenacin succinate (6 mg) and one layer of tamsulosin hydrochloride (0.4 mg).
pharmachologic effect
Vesomni - a combination product that contains two active substances, and solifsnatsin Tamsulosin. These surfactants have independent and complementary mechanisms of action in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia, in the presence of filling symptoms.
Solifenacin - selective competitive inhibitor of the bladder muscarinic receptors, mainly podtina-cubic, and has low or no affinity for various other receptors, enzymes and ion channels.
Tamsulosin - is the alpha 1-blocker. It is a selective competitive blocker postsinantichsskih ?? - adrenergic receptors, especially ?? A ?? and the D subtypes responsible for relaxation of smooth muscles of the lower urinary tract.
Pharmacokinetics
bioavailability study with repeated admission showed that the pharmacokinetics when receiving Vesomni comparable pharmacokinetics while taking solifenacin and tamsulosin Ocasio in a similar dosage.
Absorption
After multiple dose Vesomni time to maximum concentration (t max) to solifenacin ranged between 4.27 hours and 4.76 hours in different studies for tamsulosin - between 3.47 hours and 5.65 hours, respectively. The maximum plasma concentration (C max) for solifenacin varied between 26.5 ng / ml and 32.0 ng / ml, for tamsulosin - between 6.56 ng / ml and 13.3 ng / ml. The value of area under the curve "concentration-time» (AUC) for solifenacin ranged from 528 NMS / ml to 601 NMS / ml for tamsulosin - between 97.1 NMS / NMS ml and 222 / ml. The absolute bioavailability of solifenacin is about 90%, while the tamsulosin is absorbed on 70-79%.
breeding
After a single dose Vesomni half-life (T1 / 2) for solifenacin ranging from 49.5 hours to 53.0 hours for tamsulosin - from 12.8 hours to 14.0 hours.
Information about the pharmacokinetics of active substances combined preparation complements pharmacokinetic properties Vesomni:
Solifenacin
Absorption
C max is reached after 3-8 hours. t max is independent of dose. C max and AUC values ??increase proportionally to increase the dose from 5 to 40 mg. The absolute bioavailability - 90%.
Distribution
The volume of distribution of solifenacin following intravenous administration is approximately 600 l. Solifenacin significantly (about 98%) is bound to plasma proteins, with preimuscheetvenno ?? - acid glycoprotein.
Metabolism:
Solifenacin is extensively metabolised by the liver, primarily isoenzyme 3A4 (CYP3A4) cytochrome P450 system. However, there are alternative ways meetabolicheskie through which can be solifenacin metabolism. Solifenacin systemic clearance is about 9.5 liter / hour, and the terminal half-life is 45-68 hours. After oral administration of solifenacin by plasma metabolites were identified as follows: one pharmacologically active (4R-gidroksisolifenatsin) and three inactive (N-glucuronide, N-oxide and 4R-hydroxy-N-oxide solifenacin).
Excretion:
After single administration of 10 mg of 14 C-labeled solifenacin after 26 days about 70% of the radioactivity was found in the urine and 23% in feces. In urine about 11% of the radioactivity found in the unaltered form of the active substance, about 18% in the form of N-oxide metabolite, 9% as a 4R-hydroxy-N-oxide metabolite and 8% in a 4R-hydroxy metabolite (active metabolite).
Tamsulosin
Absorption
For tamsulosin in the form Ocasio absorption is estimated at 57% of the administered dose. Tamsulosin is characterized by linear pharmacokinetics. In the equilibrium state
tamsulosin in plasma concentration reaches a peak in 4-6 hours.
Distribution
Communication with plasma proteins - about 99%, volume of distribution is small (about 0.2 l / kg).
Metabolism
Tamsulosin is slowly metabolized in the liver with the formation of less active metabolites. Most of tamsulosin in plasma is presented in unmodified form. Tamsulosin is mainly metabolized by the liver, involving mainly isozymes CYP3A4 and CYP2D6.
breeding
After a single dose of 0.2 mg tamsulosin 14C-labeled 1 week 76% of the radioactivity was found in the urine and 21% in feces. In urine, about 9% of the radioactivity was found in the unaltered form of the active substance; about 16% in the form of sulfate-deetilirovannogo tamsulosin, and 8% in the form of the acetic acid-ethoxyphenoxy.
Pharmacokinetics in specific patient populations
Aged people
In studies of clinical pharmacology and bioavailability of the age of the patients ranged from 19 to 79 years. After applying Vesomni the highest rates of concentration have been identified in older patients, although there was almost complete agreement with the individual performance of the younger patients. Vesomni may be used in elderly patients.
kidney failure
Pharmacokinetics Vesomni not been studied in patients with renal insufficiency. The following data reflect the information available on each component of the drug with respect to patients with renal insufficiency.
Solifenacin
AUC and C max of solifenacin in patients with mild to moderate renal insufficiency differ slightly from those in healthy volunteers. In patients with severe renal failure (creatinine clearance <30 - = "" m = "" 30 = "" auc- = "" 100 = "" t = "" 1 = "" 2 = "" 60 = "" br = "">
tamsulosin
It compared the pharmacokinetics of tamsulosin in 6 patients with mild to moderate form of (30> creatinine clearance <70 1 = "" 73 = "" 2 = "" - = "" = 30 "" 732 = "" 6 = ""> 90 ml / min / 1,73m2). While the observed change in the total concentration of tamsulosin in blood plasma as a result of changes due to alpha 1-acid glycoprotein, tamsulosin hydrochloride active concentration and intrinsic clearance remained relatively stable. The pharmacokinetics of tamsulosin in patients with end-stage renal failure (creatinine clearance <10ml / min / 1,73m2) has not been studied.
Liver failure
Pharmacokinetics Vesomni not been studied in patients with hepatic failure. The following data reflect the information available on each component of the drug with respect to patients with hepatic insufficiency.
Solifenacin
In patients with moderate hepatic insufficiency (7-9 points on a scale Child-Pugh), the value does not change Cmax, AUC is increased by 60%, t 1/2 doubles. The pharmacokinetics in patients with severe hepatic impairment has not been determined.
tamsulosin
comparing the pharmacokinetics of tamsulosin have been conducted in 8 patients with mild hepatic insufficiency (7-9 points on a scale Child-Pugh) and in 8 healthy subjects. While the observed change in the total concentration of tamsulosin in blood plasma as a result of changes due to alpha! 1-acid glycoprotein, active concentration of tamsulosin hydrochloride does not significantly changed, and intrinsic clearance inactive tamsulosin changed moderately (32%). The pharmacokinetics of tamsulosin in patients with severe hepatic impairment has not been studied.
Side effects
Vesomni can cause side effects associated with the m-anticholinergic effect of solifenacin, usually mild or moderate severity. Most often in the course of clinical trials with Vesomni reported side effects such as dry mouth (9.5%), constipation (3.2%) and dyspepsia (including abdominal pain - 2.4%). Other common adverse reactions include dizziness (1.4%), blurred vision (1.2%), fatigue (1.2%) and ejaculatory disorders (including retrograde ejaculation - 1.5%). Acute urinary retention (0.3%, rare) - the most serious side effect, which was observed during treatment with Vesomni in clinical trials *.
* For details, see the instructions in the package.
long-term safety data Vesomni
Types and incidence of adverse reactions were observed during the treatment for 1 year Vesomni preparation were consistent with the data observed during the 12-week study. The drug was well tolerated and showed no particular adverse reactions associated with the prolonged use of the drug.
sale Properties
prescription
Special conditions
Effects on ability to drive and use machines
Studies of the effect of the drug Vesomni on ability to drive and engage in potentially hazardous activities were not carried out. However, the patient should be informed of the possible occurrence of dizziness, blurred vision, fatigue and less sleepiness, which may adversely affect the ability to drive and use machines.
testimony
Treating the symptoms of filling (irritative symptoms), moderate to strongly express (urgent urination, frequent urination), and voiding symptoms (obstructive symptoms) associated with benign prostatic hyperplasia in men.
Contraindications
hemodialysis
Severe hepatic insufficiency
Severe renal impairment or moderate hepatic impairment, while the treatment of potent inhibitors of CYP3A4 izofsrmsnta, such as ketoconazole
The presence of severe diarrheal disease (including toxic megacolon), myasthenia gravis, and angle-closure glaucoma
Orthostatic hypotension
Children under 18 years of age (lack of efficacy and safety data)
Carefully
Vesomni should be used with caution in patients with: severe renal insufficiency, the risk of urinary retention, gastrointestinal obstructive disorders, the risk of reduced motility of the gastrointestinal tract,
with a hiatal hernia, gastroesophageal reflux and patients simultaneously receiving drugs (such as bisphosphonates) that can cause or exacerbate esophagitis, with autonomic neuropathy in patients with such risk factors as extension syndrome QT interval and hypokalemia, there was a prolongation of the interval QT and tachycardia type "pirouette".
Some patients treated with solifenacin after the registration of the drug, has been marked by an anaphylactic reaction. With the development of anaphylactic reactions Vesomni treatment should be discontinued and appropriate treatment is necessary.
As with other ?? - blockers in the treatment of tamsulosin in some cases there may be a decrease in blood pressure, which in
rare cases may cause fainting. At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down and remain in that position for as long as the symptoms do not disappear.
Some patients taking or previously treated with tamsulosin hydrochloride, during surgery for cataract and glaucoma noted the development of the iris syndrome intraoperative instability eyes (narrow pupil syndrome), which can lead to complications during surgery or in the postoperative period. It is not recommended to start Vesomni therapy in patients scheduled for cataract surgery and glaucoma. Expediency discontinuation Vesomni 1-2 weeks prior to cataract surgery and glaucoma has not yet been proved. During the preoperative evaluation of patients surgeon and ophthalmologist should consider taking or whether the patient took Vesomni. It is necessary to prepare for the possible development of the operation, intraoperative instability syndrome iris.
Vesomni should be used with caution in combination with potent inhibitors of CYP3A4 and moderate, for example, verapamil, ketoconazole, ritonavir, nelfinavir, itraconazole. The drug should not be used in patients with impaired metabolism of CYP2D6 isozyme in combination with potent inhibitors of CYP3A4 or CYP2D6 potent inhibitors, such as paroxetine.
Patients with renal failure
Vesomni can be used by patients with mild to moderate renal impairment, but caution should be used in patients with severe renal insufficiency.
Patients with hepatic insufficiency
Vesomni can be used by patients with mild hepatic insufficiency (on a scale Child-Pugh score <7). Patients with moderate hepatic insufficiency (7-9 points on a scale Child-Pugh) should be taken with caution. Patients with severe hepatic impairment (score on the Child-Pugh above 9) The use of Vesomni contraindicated.
Application of pregnancy and during breast-feeding, the effect on fertility
Vesomni Effects on reproductive function has not been studied. Animal studies revealed no direct adverse effects of solifenacin and tamsulosin on fertility or development of the embryo / fetus.
Pregnancy and lactation
Vesomni The drug is intended for use only in males.
Drug interactions
Interaction with inhibitors of CYP3A4 and CYP2D6
The simultaneous use of solifenacin and ketoconazole (200 mg daily), a potent inhibitor of isozyme CYP3A4. It caused a doubling of solifenacin AUC, and 400 mg / day - fold increase.
Simultaneous application Tamsulosin ketoconazole at a dose of 400 mg / day increases Cmax and AUC tamsulosin 2.2 and 2.8 times respectively.
Simultaneous reception Vesomni with verapamil (a moderate inhibitor of CYP3A4) increases Cmax and AUC of tamsulosin 2.2-fold increase in Cmax and AUC of solifenacin and approximately 1.6 times.
Simultaneous administration of tamsulosin with a strong CYP2D6 inhibitor paroxetine (20 mg / day) increases the Cmax and AUC of tamsulosin 1.3 and 1.6 times, respectively.
Since solifenacin and tamsulosin metabolized isoenzyme of CYP3A4, pharmacokinetic interactions are possible with isoenzyme inducers of CYP3A4 (eg, rifampicin).
Other interactions
Solifenacin
Solifenacin can reduce the effect of drugs that stimulate the motility of the gastrointestinal tract, for example - metoclopramide and cisapride.
Studies in vitro have shown that therapeutic concentrations solifenacin not inhibit isozymes CYP1A1 / 2, 2B6, 2S8, 2S9, 2C19, 2D6, 2E1 or ZA4. therefore
it is unlikely that drugs alter solifenacin clearance izoCYP-metabolizable these enzymes.
Admission solifenacin did not cause changes in the pharmacokinetics of R-warfarin and S-warfarin or their effect on prothrombin time.
Admission solifenacin no effect on the pharmacokinetics of digoxin.
tamsulosin
Co-administration of other a1-adrenergic blockers could lead to hypotensive effects.
Diazepam, propranolol, trichloromethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin and warfarin does not alter tamsulosin free fraction in human plasma in vitro. In turn, serves as tamsulosin free fractions of diazepam, propranolol, trichlormethiazide and chlormadinone. Diclofenac and Warfarin may increase the elimination rate of tamsulosin.
While the use of furosemide was a slight reduction in the concentration, however, it does not require a change in dose, since the drug concentration is within the normal range.
Studies in vitro have shown that therapeutic concentrations tamsulosin does not inhibit isozymes CYP1A1 / 2, 2C9, 2C19, 2D6, 2E1 or ZA4. Therefore, it is unlikely that drugs tamsulosin alter clearance izoCYP-metabolizable these enzymes.
In the appointment of tamsulosin with atenolol, enalapril or theophylline interactions were found.
