Vesomni mv film-coated pills 6 mg + 0.4 mg N30
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Active ingredients
Tamsulosin + Solifenacin
Release form
Pills
Composition
1 caps tamsulosin hydrochloride 400 mcg Auxiliary substances: microcrystalline cellulose - 281.2 mg, copolymer of methacrylic acid and ethyl acrylate - 42.5 mg, polysorbate 80 - 1 mg, sodium lauryl sulfate - 0.3 mg, triacetin - 1.1 mg, talc - 0.8 mg, calcium stearate - 0.4 mg. The composition of the capsule shell *: gelatin - 62.8 mg, titanium dioxide - 0.89 mg, indigo carmine - 0.004 mg, iron dye yellow oxide - 0.5 mg, iron dye red oxide - 0.04 mg.
Pharmacological effect
The mechanism of action of Vesomne is a combination drug that contains two active substances, solifenacin and tamsulosin. These active substances 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 is a selective competitive inhibitor of the muscarinic receptors of the bladder, mainly the M3 subtype, and has low or no affinity for various other receptors, enzymes, and ion channels. Tamsulosin is an alpha1-blocker. It is a selective competitive blocker of postsynaptic α1-adrenoreceptors, especially the α1 and α1D subtypes, which are responsible for relaxing the smooth muscles of the lower urinary tract. Pharmacodynamic effects Solifenacin relieves bladder filling symptoms (irritative symptoms) associated with the action of acetylcholine, which activates the m3-cholinergic receptors in the bladder. Acetylcholine activates the contractile function of the bladder wall, which manifests itself as an urgent urge to urinate or urinary incontinence. Tamsulosin relieves emptying symptoms (obstructive symptoms) by relaxing the smooth muscles of the prostate gland, bladder neck and the prostatic part of the urethra. Also reduces filling symptoms. Clinical efficacy and safety The efficacy of the drug was demonstrated as a result of a phase III clinical trial in patients with lower urinary tract symptoms in the presence of benign prostatic hyperplasia. When taking Vesomni, a statistically significant decrease in symptoms was noted on the scale of urge urgency and frequency of urination,as well as the general frequency of urination, the average volume of urine allocated for one urination, and the score on the baseline of the IPSS-filling compared to Omnik OKAS (tamsulosin in the form of controlled release; OCAS - oral controlled absorption system / OKAC - oral system of controlled absorption). These improvements are accompanied by a significant increase in the indicator of quality of life on the IPSS scale and the indicator of quality of life according to the Questionnaire for assessing the severity of bladder hyperactivity symptoms. In addition, Vesomni was not inferior to tamsulosin Omnic Ocas in reducing symptoms when evaluating the overall score on the IPSS scale (less than 0.001).
Pharmacokinetics
A bioavailability study with repeated intake showed that the pharmacokinetics when taking Vesomni is comparable to the pharmacokinetics while taking solifenacin and tamsulosin OKAS in the same dosage. Absorption After repeated administration of Vesomne, Tmax for solifenacin varied between 4.27 h and 4.76 h in different studies, for tamsulosin - between 3.47 h and 5.65 h, respectively. Plasma Cmax 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 AUC value for solifenacin ranged from 528 ngch / ml to 601 ngch / ml, for tamsulosin - between 97.1 ngch / ml and 222 ngch / ml. Absolute bioavailability for solifenacin is about 90%, while tamsulosin is absorbed by 70-79%. Withdrawal After a single dose of Vesomne T1 / 2 for solifenacin ranges from 49.5 h to 53.0 h, for tamsulosin from 12.8 h to 14.0 h. Information on the pharmacokinetics of the active substances of the combined preparation complements the pharmacokinetic properties of Vesomni: Solifenacin Cmax is reached after 3-8 h. Tmax independent of dose Cmax and AUC increase in proportion to the dose increase from 5 to 40 mg. Absolute bioavailability - 90%. The Vd distribution of solifenacin after IV injection is approximately 600 liters. Solifenacin is largely (about 98%) bound to plasma proteins, predominantly with an α1-acid glycoprotein. Metabolism Solifenacin is actively metabolized by the liver, predominantly by the 3A4 (CYP3A4) isoenzyme of the cytochrome P450 system. However, there are alternative metabolic pathways through which solifenacin may be metabolized. The systemic clearance of solifenacin is about 9.5 l / h, and the final T1 / 2 is 45-68 h.After taking the drug inside the plasma by solifenacin, the following metabolites were identified: one pharmacologically active (4R-hydroxysolifenacin) and three inactive N-glucuronide, N-oxide and 4H-hydrosy-N-oxide solifenacin). Withdrawal After a single injection of 10 mg of 14C-labeled solifenacin after days, about 70% of the radioactivity was detected in the urine and 23% in the feces. In the urine, approximately 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). Tamsulosin Absorption For tamsulosin in the form of OKAS absorption is estimated at 57% of the administered dose. Tamsulosin is characterized by linear pharmacokinetics. In equilibrium, the concentration of tamsulosin in the plasma reaches a peak after 4-6 hours. Distribution Communication with plasma proteins is about 99%, Vd is small (about 0.2 l / kg). Metabolism Tamsulosin is slowly metabolized in the liver to form less active metabolites. Most tamsulosin is present in plasma in unchanged form. Tamsulosin is mainly metabolized in the liver, mainly with the participation of CYP3A4 and CYP2D6 isoenzymes. Withdrawal After a single dose of 0.2 mg of 14C-labeled tamsulosin after 1 week, about 76% of the radioactivity was detected in the urine and 21% in the feces. In the urine, about 9% of the radioactivity was detected as unchanged active substance; about 16% as sulphate of o-deethyl tamsulosin, and 8% as o-ethoxyphenoxy acetic acid. Features of pharmacokinetics in certain categories of patients Older people In clinical pharmacology and bioavailability studies, the age of patients ranged from 19 to 79 years. After Vesomni was applied, the highest concentrations were found in elderly patients, although there was an almost complete decrease with some indicators of younger patients. Vesomes can be used in older patients. Renal Failure The pharmacokinetics of Vesomnia has not been studied for patients with renal insufficiency. The data below reflects information available for each component of the preparation regarding patients with renal insufficiency. Solifenacin AUC and Cmax solifenacin in patients with mild to moderate renal failure differ slightly from those in healthy volunteers.In patients with severe renal insufficiency (CK ≤ 30 ml / min), the exposure of solifenacin is much higher - the increase in Cmax is about 30%, the AUC is more than 100% and T1 / 2 is more than 60%. A statistically significant relationship between QA and clearance of solifenacin was noted. Pharmacokinetics in patients undergoing hemodialysis has not been studied. Tamsulosin Tamsulosin pharmacokinetics were compared in 6 patients with mild and moderate form (30≥KK less than 70 ml / min / 1.73 m2) or moderately severe form (≤ 30 ml / min / 1.73 m2) of renal failure and in 6 healthy patients ( QC ≥90 ml / min / 1.73 m2). While there was a change in the total concentration of tamsulosin in the blood plasma as a result of a change in association with alpha 1-acid glycoprotein, the active concentration of tamsulosin hydrochloride, as well as its own clearance, remained relatively stable. The pharmacokinetics of tamsulosin in patients with the last stage of renal failure (CC less than 10 ml / min / 1.73 m2) has not been studied. Hepatic insufficiency The pharmacokinetics of Vesomney has not been studied for patients with hepatic insufficiency. The data below reflects information available for each component of the preparation regarding patients with hepatic insufficiency. Solifenacin In patients with moderate hepatic impairment (7–9 points on the Child-Pugh scale), Cmax does not change, AUC increases by 60%, T1 / 2 doubles. Pharmacokinetics in patients with severe hepatic insufficiency was not determined. Tamsulosin Tamsulosin pharmacokinetics were compared in 8 patients with moderate hepatic impairment (7–9 on the Child-Pugh scale) and in 8 healthy patients. While a change in total plasma concentration of tamsulosin was observed as a result of a change in association with alpha-1 acid glycoprotein, the active concentration of tamsulosin hydrochloride did not change significantly, and its own clearance of inactive tamsulosin was moderately changed (32%). The pharmacokinetics of tamsulosin in patients with severe hepatic insufficiency ns has been studied.
Indications
treatment of filling symptoms (irritative symptoms), moderate to severe (urge to urinate, frequent urination), and emptying symptoms (obstructive symptoms) associated with benign prostatic hyperplasia in men.
Contraindications
hypersensitivity to the active substances or any of the auxiliary substances; hemodialysis; severe liver failure; severe renal insufficiency or moderate hepatic insufficiency with simultaneous treatment with strong inhibitors of the CYP3A4 isoenzyme, for example, ketoconazole; the presence of severe gastrointestinal diseases (including toxic megacolon), myasthenia and angle-closure glaucoma; orthostatic hypotension; children's age up to 18 years (lack of data on efficiency and safety). With caution Vesomny should be used with caution in patients with: severe renal insufficiency; risk of urinary retention; gastrointestinal obstructive diseases; risk of reduced gastrointestinal motility; with hernia of the esophageal opening of the diaphragm, gastroesophageal reflux, and patients simultaneously taking drugs (for example, bisphosphates) that can cause or strengthen esophagitis; with autonomic neuropathy; in patients with such risk factors as a syndrome of lengthening the QT interval and hypokalemia, prolongation of the QT interval and tachycardia such as pirouette were observed. Anaphylactic reaction was noted in some patients who received treatment with solifenacin after registering the drug. With the development of anaphylactic reactions, the treatment should be stopped and appropriate treatment should be carried out. As with other alpha1-adrenergic blockers, with treatment with tamsulosin, in some cases, a decrease in blood pressure can be observed, which in rare cases can lead to fainting. At the first sign of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down and remain in this position until the signs disappear. Some patients taking or previously taking tamsulosin hydrochloride, during surgery but about cataracts and glaucoma, have developed the syndrome of intraoperative iris instability (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 who are scheduled for cataract or glaucoma surgery.The expediency of discontinuing Vesomni therapy 1-2 weeks before cataract or glaucoma surgery is still not proven. During the preoperative examination of patients, the surgeon and the ophthalmologist should consider whether this patient is accepting or accepting Vesomni. This is necessary to prepare for the development of the syndrome of intraoperative instability of the iris. Vesomni should be used with caution in combination with strong and moderate CYP3A4 inhibitors, for example, verapamil, ketoconazole, ritonavir, nelfinavir, itraconazole. The drug should not be used in patients with metabolic imbalance of CYP2D6 isoenzyme in combination with strong inhibitors of CYP3A4 or strong inhibitors of CYP2D6, for example, paroxetine. Patients with renal insufficiency Vesomne can be used in patients with mild to moderate renal insufficiency, but should be used with caution in patients with severe renal insufficiency. Patients with hepatic insufficiency Vesomney can be used by patients with mild hepatic insufficiency (Child-Drink score ≤7). Patients with moderate hepatic insufficiency (7–9 points on the Child-Pugh scale) should take the drug with caution. Patients with severe hepatic insufficiency (score on the Child-Pugh scale above 9) use Vesomni contraindicated.
Precautionary measures
Application for violations of liver function. The drug is used with caution in patients with moderate hepatic insufficiency (7-9 points on the Child-Pugh scale). Patients with severe hepatic insufficiency (Child-Pugh score above 9) are contraindicated. used in patients with mild and moderate renal insufficiency, but with caution should be used in patients with severe renal insufficiency. The drug is contraindicated in patients with severe Aloe renal failure or moderate hepatic insufficiency with simultaneous treatment with strong inhibitors of the CYP3A4 isoenzyme, for example, ketoconazole. Use in children The drug is contraindicated in children and adolescents under the age of 18 years.
Use during pregnancy and lactation
The impact of Vesomny on reproductive function has not been studied.Animal studies have not revealed a direct adverse effect of solifenacin or tamsulosin on fertility or embryo / fetus development. Pregnancy and lactation Vezomni drug is intended for use only in males.
Dosage and administration
Adults over the age of 18, as well as elderly patients Inside, 1 tab. 1 time / day, regardless of the meal. The tablet must be taken whole, it can not be chewed, because This may affect the prolonged release of the active substance.
Side effects
Vesomnia can cause side effects associated with the m-anticholinergic action of solifenacin, often mild or moderate severity. The most frequently reported side effects of dry mouth (9.5%), constipation (3.2%) and dyspepsia (including 2.4% pain in the abdomen) were reported during the conduct of clinical trials with Vesomni. Other common adverse reactions include dizziness (1.4%), blurred vision (1.2%), fatigue (1.2%), and ejaculation disorders (including retrograde ejaculation - 1.5%). Acute urinary retention (0.3%, rare) is the most serious side effect that was observed during the treatment with Vesomni during clinical trials.
Overdose
Overdose with a combination of solifenacin and tamsulosin may be accompanied by severe m-holinoblokiruyuschimi violations along with acute hypotension. The highest dose that was taken by chance during a clinical trial was 126 mg solifenacin and 5.6 mg tamsulosin. This dose was well tolerated, it was noted the only undesirable phenomenon - dry mouth weak degree of severity for 16 days. Treatment In cases of overdose, activated charcoal should be prescribed, the stomach should be flushed, but vomiting should not be induced. As in cases of overdose of other m-cholinoblockers, the symptoms should be treated as follows: - for severe m-anticholinergic effects of a central action (hallucinations, marked excitability) - physostigmine or activated carbon; - for convulsions or marked irritability - benzodiazepines; - in respiratory failure - artificial respiration; - with tachycardia - symptomatic treatment as needed.Beta-blockers should be used with caution, since simultaneous overdose with tamsulosin can potentially lead to severe hypotension; - during acute urinary retention - catheterization. As in the case of overdose of other m-cholinoblockers, special attention should be paid to patients with an established risk of lengthening the QT interval (ie, with hypokalemia, bradycardia and while taking medications that cause lengthening of the QT interval) and patients with heart disease (myocardial ischemia, arrhythmias, chronic heart failure). Severe hypotension that may occur after a tamsulosin overdose should be treated symptomatically. It is unlikely that dialysis will be effective, because tamsulosin is intensively bound to plasma proteins.
Interaction with other drugs
Interaction with CYP3A4 and CYP2D6 inhibitors The simultaneous use of solifenacin and ketoconazole (200 mg / day), a potent inhibitor of the CYP3A4 isoenzyme, caused a twofold increase in the AUC of solifenacin, and at a dose of 400 mg / day - a threefold increase. The simultaneous use of tamsulosin with ketoconazole at a dosage of 400 mg / day leads to an increase in Cmax and AUC of tamsulosin by 2.2 and 2.8 times, respectively. Simultaneous administration of Vesomni with verapamil (a moderate CYP3A4 inhibitor) leads to an increase in Cmax and AUC of tamsulosin by 2.2 times and an increase in Cmax and AUC of solifenacin by about 1.6 times. The simultaneous administration of tamsulosin with a strong CYP2D6 inhibitor paroxetine (20 mg / day) leads to an increase in Cmax and AUC of tamsulosin by 1.3 and 1.6 times, respectively. Since solifeiatsin and tamsulosin are metabolized by CYP3A4 isoenzyme, pharmacokinetic interactions with inducers of CYP3A4 isoenzyme (for example, rifampicin) are possible. Other interactions Solifenacin - Solifenacin may reduce the effect of drugs that stimulate GI motility, for example, metoclopramide and cisapride. - In vitro studies have shown that at therapeutic concentrations, solifenacin does not inhibit CYP1A1 / 2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 isoenzymes. Therefore, it is unlikely that solifenacin will change the clearance of drugs metabolized by these isoCYP enzymes. - The administration of solifenacin ns caused changes in the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time. - The administration of solifenacin does not affect the pharmacokinetics of digoxin.Tamsulosin - Simultaneous administration of other α1-adrenoreceptor blockers can lead to a hypotensive effect. - Diazepam, propranolol, trichlormethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin and warfarin do not change the free fraction of tamsulosin in human plasma in vitro. In turn, tamsulosin also does not change the free fractions of diazepam, propranolol, trichloromethiazide and chlormadinone. Diclofenac and warfarin may increase the rate of elimination of tamsulosin. - When used simultaneously with furosemide, a slight decrease in concentration is noted, but this does not require a dose change, since the drug concentration remains within the normal range. - In vitro studies have shown that at therapeutic concentrations, tamsulosin does not inhibit CYP1A1 / 2, 2C9, 2C19, 2D6, 2E1 or 3A4 isoenzymes. Therefore, it is unlikely that tamsulosin will change the clearance of drugs metabolized by these iso-SUR enzymes. - When prescribing tamsulosin together with atenolol, enalapril or theophylline interactions, ns was detected.
special instructions
Impact on the ability to drive vehicles and mechanisms Studies on the effects of Vesomni on the ability to drive vehicles and engage in potentially hazardous activities have not been conducted. However, the patient should be informed about the possible occurrence of dizziness, blurred vision, fatigue and less sleepiness, which can adversely affect the ability to drive and work with mechanisms.