Soliksa-Xantis pills 10mg, 60pcs

Composition

1 film-coated tablet,10 mg contains:

Active ingredient:

solifenacin succinate – 10.00 mg;

auxiliary substances:

lactose monohydrate – 110,50 mg,

corn starch – 30,00 mg,

talc – 3,00 mg,

magnesium stearate – 1,50 mg;

film shell: Opadry white 03B28796 – 3,60 mg (hypromellose 6cP E464 – 2,2500 mg, titanium dioxide E 171 – 1,1250 mg, macrogol 400 – 0,2250 mg), Opadry brown 02F 23883 – 0,40 mg (hypromellose 5 cP E464 – 0,2374 mg, titanium dioxide E 171 – 0,0895 mg macrogol 6000 – 0,0475 mg, dye iron oxide yellow E 172 – 0,0128 mg, dye iron oxide red E 172 – 0,0128).

Pharmacological action

Pharmacotherapeutic group: drugs for the treatment of frequent urination and urinary incontinence, antispasmodic agent.

ATX CODE: G04BD08

Pharmacological properties

Mechanism of action

Solifenacin is a specific competitive muscarinic receptor antagonist. The bladder is innervated by parasympathetic cholinergic nerves. Acetylcholine acts on muscarinic receptors (mainly_M3) and causes detrusor contraction Pharmacological studies conductedin vitro and in vivo have shown that solifenacin is a specific competitive inhibitor of muscarinic receptors_{of the M3 subtype}. Solifenacin has also been found to have low or no affinity for various other receptors and ion channels.

Pharmacodynamics

The clinical effect of solifenacin in doses of 5 mg and 10 mg is observed already during the first week of treatment and stabilizes over the next 12 weeks of treatment. The effectiveness is maintained for at least 12 months. The maximum effect of solifenacin is observed 4 weeks after the start of therapy.

Pharmacokinetics

Absorption rate: the maximum plasma concentration (with_max) is reached after 3-8 hours. The time to reach the maximum concentration (tmax) does not depend on the dose. With_max and the area under the curve (AUC) of the concentration versus time dependence increase in proportion to the dose increase from 5 to 40 mg. Absolute bioavailability is 90%. Food intake does not affect the C_max and AUC of solifenacin.

Distribution: the volume of distribution of solifenacin after intravenous use is approximately 600 liters. Solifenacin binds significantly (about 98%) to plasma proteins, mainly with_α1-acid glycoprotein.

Metabolism: solifenacin is extensively metabolized by the liver, mainly by the CYP3A4 isoenzyme. However, there are alternative metabolic pathways through which solifenacin can be metabolized. The systemic clearance of solifenacin is about 9.5 l / h, and the final half-life is 45-68 hours. After oral use, the following metabolites were identified in plasma in addition to solifenacin: one pharmacologically active(4R-hydroxysolifenacin) and three inactive (N-glucuronide, N-oxide and 4R-hydroxy-N-oxide of solifenacin).

Elimination: after a single use of 10 mg of 14C-labeled solifenacin after 26 days, about 70% of radioactivity was detected in the urine and 23% in the faeces. In the urine, approximately 11% of radioactivity was detected as an unchanged Active ingredient, about 18% as an N-oxide metabolite,9% as a 4R-hydroxy-N-oxide metabolite, and 8% as a 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 patient’s age. Studies have shown that solifenacin exposure (5 and 10 mg), expressed as AUC, was similar in healthy elderly volunteers (65 to 80 years) and in healthy young volunteers (

The average absorption rate expressed as tmax was slightly lower, and the terminal half-life was approximately 20% longer in older adults. These minor differences are not clinically significant.

The pharmacokinetics of solifenacin have not been determined in children and adolescents.

Gender: The pharmacokinetics of solifenacin are independent of the patient’s gender.

Race: Race does not affect the pharmacokinetics of solifenacin.

Renal insufficiency: The AUC and_cmax of solifenacin in patients with mild to moderate renal insufficiency differ slightly from the corresponding values in healthy volunteers. In patients with severe renal insufficiency (creatinine clearance <30 ml/min), solifenacin exposure is significantly higher – an increase_{in max} is about 30%, AUC is more than 100%_{, and 1/2} is more than 60%. There was a statistically significant relationship between creatinine clearance and solifenacin clearance. Pharmacokinetics in patients undergoing hemodialysis have not been studied.

Liver failure: In patients with moderate hepatic insufficiency (Child-Pugh stage B), the C_{max value} does not change, AUC increases by 60%, and T_1/2 doubles. Pharmacokinetics in patients with severe hepatic insufficiency were not determined.

Indications

Symptomatic treatment of urinary incontinence, frequent urination and urgent urge to urinate in patients with overactive bladder syndrome.

Use during pregnancy and lactation

There are no clinical data on women who became pregnant while taking solifenacin. Animal studies have shown no direct adverse effects on fertility, embryo/fetus development, or delivery. Solifenacin can only be used during pregnancy if the benefit of therapy to the mother exceeds the potential risk to the fetus.

There are no data on the penetration of solifenacin into human breast milk. In animal studies, solifenacin and / or its metabolites were found to enter the milk of lactating mice. The use of solifenacin is contraindicated during breastfeeding.

Contraindications

• delay urination;
• severe gastrointestinal disease (including toxic megacolon);
• myasthenia gravis;
• angle-closure glaucoma;
• hypersensitivity to solifenacin or any of the excipients;
• the hemodialysis;
• hepatic failure, severe;
• renal failure or severe liver failure of moderate severity while treatment with strong inhibitors of CYP3A4, such as ketoconazole (see section “Interaction with other medicines”);
• lactase deficiency, lactose intolerance, a syndrome of glucose-galactose malabsorption;
• the period of breast-feeding (see “pregnancy and breastfeeding”)
• children under 18 years of age.

With caution

Other causes of frequent urination (such as chronic heart failure or kidney disease) should be excluded before starting solifenacin therapy. If a urinary tract infection is detected, appropriate antibacterial therapy should be performed. Compliance with precautions when using solifenacin is required in patients:

• with clinically significant obstruction of the outlet of the bladder, leading to the risk of urinary retention;
• with gastrointestinal disease with obstruction;
• with the risk of reduced motility of the gastrointestinal tract;
• with renal insufficiency, severe (creatinine clearance <30 ml / min) and liver failure of moderate severity (stage according To the classification of child-Pugh); the dose for these patients should not exceed 5 mg;
• at the same time receiving strong inhibitors of CYP3A4, such as ketoconazole;
• hernia hiatal, gastroesophageal reflux or patients concurrently taking drugs (e. g. bisphosphonates) that can cause or exacerbate esophagitis;
• with autonomic neuropathy;

in women during pregnancy (see section “pregnancy and breastfeeding”).

Side effects

The use of solifenacin may cause undesirable reactions associated with its anticholinergic effect, most often of mild or moderate severity. The frequency of these adverse reactions depends on the dose of solifenacin. The most frequently reported adverse reaction of solifenacin 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% of patients receiving placebo. The severity of dry mouth was usually mild and only rarely led to discontinuation of treatment.

Immune system disorders: anaphylactic reactions

Metabolic and nutritional disorders: decreased appetite, hyperkalemia

Mental disorders: hallucinations, confusion, delirium

Gastrointestinal disorders: dry mouth, constipation, nausea, dyspepsia, abdominal pain, gastroesophageal reflux disease, dry throat, colonic obstruction, coprostasis, vomiting, ileus, abdominal discomfort

Liver and biliary tract disorders: liver disorders, changes in liver function tests

Infectious and parasitic diseases: urinary tract infection, cystitis

Nervous system disorders: drowsiness, dysgeusia( taste disorder), dizziness, headache

Disorders of the visual organ: blurred vision (violation of accommodation), dryness of the eye mucosa, glaucoma

Cardiac disorders: pirouette-type ventricular tachycardia, prolongation of the QT interval (ECG), atrial fibrillation, tachycardia, palpitation sensation

General disorders and disorders at the injection site: fatigue, peripheral edema

Respiratory, thoracic and mediastinal disorders: dryness of the nasal cavity, dysphonia

Skin and subcutaneous tissue disorders: dry skin, rash, pruritus, erythema multiforme, urticaria, angioedema, exfoliative dermatitis

Musculoskeletal and connective tissue disorders: muscle weakness

Disorders of the kidneys and urinary tract: difficulty urinating, urinary retention, renal failure

Interaction

Pharmacological interaction

Concomitant treatment with drugs with anticholinergic properties may lead to more pronounced pharmacological effects and undesirable reactions. After stopping taking solifenacin, you should take a break of approximately one week before starting treatment with another anticholinergic drug. The pharmacological effect may be reduced with concomitant use of cholinergic receptor agonists. Solifenacin may reduce the effect of medications that stimulate gastrointestinal motility, such as metoclopramide.

Pharmacokinetic interaction

In vitro studies have shown that at therapeutic concentrations, solifenacin does not inhibit CYP1A1/2,2C9,2C19,2D6 or ZA4 isoenzymes isolated from human liver microsomes. Therefore, it is unlikely that solifenacin will alter the clearance of drugs metabolized by these CYP enzymes.

Effects of other drugs on the pharmacokinetics of solifenacin

Solifenacin is metabolized by the CYP3A4 isoenzyme. Concomitant use of ketoconazole (200 mg / day), a strong inhibitor of the CYP3A4 isoenzyme, caused a twofold increase in the AUC of solifenacin concentration versus time, and a three – fold increase at a dose of 400 mg/day. Therefore, the maximum dose of solifenacin should not exceed 5 mg if the patient is simultaneously taking ketoconazole or therapeutic doses of other strong inhibitors of the CYP3A4 isoenzyme (such as ritonavir, nelfinavir, itraconazole). Concomitant use of solifenacin and strong inhibitors of the CYP3A4 isoenzyme is contraindicated in patients with severe renal insufficiency or moderate hepatic insufficiency. The effects of enzyme induction on the pharmacokinetics of solifenacin and its metabolites, as well as the effect of high-affinity substrates of the CYP3A4 isoenzyme on the action of solifenacin, have not been studied.

Since solifenacin is metabolized by the CYP3A4 isoenzyme, pharmacokinetic interactions with other substrates of the CYP3A4 isoenzyme with higher affinity (verapamil, diltiazem) and with inducers of the CYP3A4 isoenzyme (rifampicin, phenytoin, carbamazepine) are possible.

Effect of solifenacin on the pharmacokinetics of other drugs

Oral contraceptives: there was no pharmacokinetic interaction between solifenacin and combined oral contraceptives (ethinyl estradiol+levonorgestrel).

Warfarin: solifenacin use did not cause changes in the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.

Digoxin: solifenacin did not affect the pharmacokinetics of digoxin.

How to take, course of use and dosage

Adults, including the elderly

5 mg once a day inside, whole, washed down with liquid, regardless of the time of meal. If necessary, the dose can be increased to 10 mg once a day.

Children

The safety and efficacy of solifenacin in children have not been studied, and therefore the use of Solixa-Xanthis in children is contraindicated.

Patients with renal insufficiency

No dose adjustment is required in patients with mild to moderate renal insufficiency (creatinine clearance > 30 ml / min). In patients with severe renal insufficiency (creatinine clearance

Patients with hepatic insufficiency

No dose adjustment is required in patients with mild hepatic insufficiency. In patients with moderate hepatic insufficiency (Child-Pugh stage B), Solixa-Xanthis should be used under close medical supervision and at a dose of no more than 5 mg per day.

Patients receiving strong inhibitors of the CYP3A4 isoenzyme

When solifenacin is co-administered with ketoconazole or a therapeutic dose of another strong inhibitor of the CYP3A4 isoenzyme, such as nelfinavir itraconazole, the maximum daily dose of Solix-Xanthis should not exceed 5 mg.

Overdose

An overdose of solifenacin can potentially lead to severe anticholinergic effects. The highest dose of solifenacin that was accidentally taken by one patient was 280 mg over 5 hours. This dose resulted in a change in the patient’s mental state, but did not require hospitalization. In cases of overdose, activated charcoal should be prescribed, gastric lavage is effective for an hour, but vomiting should not be induced. As with overdoses of other anticholinergic agents, symptoms should be treated as follows::

• for severe central anticholinergic effects (hallucinations, severe excitability) – carbachol;
• for convulsions or severe excitability-benzodiazepines;
• for respiratory failure-artificial respiration;
• for tachycardia-beta-blockers;
• for acute urinary retention-catheterization;
• for mydriasis-instill pilocarpine in the eyes and / or place the patient in a dark room.

As in the case of overdose with other anticholinergic drugs, special attention should be paid to patients with an established risk of prolongation of the QT interval (i. e., with hypokalemia, bradycardia and concomitant use of drugs that cause prolongation of the QT interval) and patients with previously identified heart diseases (myocardial ischemia, arrhythmias, chronic heart failure).

Description

Film-coated tablets,10 mg

Round, biconvex tablets, covered with a film-coated pink color.

Special instructions

In patients with risk factors such as existing QT prolongation and hypokalemia, QT prolongation and ventricular tachycardia of the “pirouette” type were observed. Efficacy and safety have not been studied in patients with neurogenic bladder dysfunction. There have been several cases of angioedema with airway obstruction in patients taking solifenacin. Therefore, if angioedema occurs, solifenacin should be discontinued and appropriate measures taken.

Several cases of anaphylactic reactions have been reported in patients taking solifenacin. Therefore, if an anaphylactic reaction occurs, solifenacin should be discontinued and appropriate measures taken.

Influence on the ability to drive vehicles and mechanisms

Solifenacin, like other anticholinergic drugs, can cause blurred vision, as well as (rarely) drowsiness and fatigue, which can negatively affect the ability to drive a car and work with mechanisms.

Form of production

10 tablets in oPA/Al/PVC / Al blister.

By 1,2,3,5,6,9 or 10 blisters together with the instructions for use in a cardboard box.

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 4 years. Do not use after the expiration date.

Active ingredient

Solifenacin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets