Pharmacological studies winstrol reviews conducted in vitro and in vivo, have shown that solifenacin is a specific competitive inhibitor of muscarinic receptors, especially the M 3subtype. Also, it was found that solifenacin has low or no affinity for various other receptors and ion channels. Efficacy Vesicare in doses winstrol reviews of 5 mg and 10 mg, studied in several double-blind, randomized, controlled clinical trial on men and women with the syndrome of Overactive Bladder It was observed as early as the first week of treatment and stabilized over the next 12 weeks of treatment. Vesicare maximum effect can be detected after 4 weeks. Efficiency is maintained for a long use (at least – 12 months).
Maximum plasma concentration (C max ) is achieved after 3-8 hours. The time to reach maximum concentration (t max ) is independent of dose. C max and the area under the curve (AUC) of concentration vs. time increase proportionally to dose increase from 5 to 40 mg. The absolute bioavailability – 90%. Food intake does not affect the C max and AUC of solifenacin. Distribution: The volume of distribution of solifenacin following intravenous administration is about 600l. Solifenacin significantly (about 98%) is bound to plasma proteins, mainly to α 1 -kislym glycoprotein.Metabolism Solifenacin is extensively metabolised by the liver, primarily by cytochrome P450 ZA4 (CYP3A4). However, there are alternative pathways 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 in plasma in addition to solifenacin these metabolites have been identified: one pharmacologically active (4R-gidroksisolifenatsin) and three inactive (N-glucuronide, N-oxide and 4R-hydroxy-N-oxide solifenacin). Excretion: After a single injection of 10 mg 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 form of unmodified active ingredient, 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). Pharmacokinetics solifenacin is linear in the therapeutic dose range. pharmacokinetics in specific patient populations Age: No need to adjust the dose depending on the age of patients. Studies have shown that exposure of solifenacin (5 and 10 mg), expressed as the AUC, was similar in healthy elderly individuals (65 to 80 years) and healthy young individuals (<55 years). The average rate of absorption expressed as t max . It was somewhat lower and the terminal half-life approximately 20% longer in the elderly. These minor differences are not clinically significant. The pharmacokinetics of solifenacin are not determined in children and adolescents. Sex: Pharmacokinetics of solifenacin does not depend on the patient’s sex. Race: Race does not affect the pharmacokinetics of solifenacin. Renal failure: the AUC and C max of solifenacin winstrol results in patients with mild to moderate renal insufficiency differ slightly from those in healthy volunteers. In patients with severe renal insufficiency (creatinine clearance <30 mL / min), solifenacin exposure is much higher – an increase in C max is around 30%, PPC – more than 100% and t 1/2 – more than 60%. There was a statistically significant correlation between creatinine clearance and solifenacin clearance. The pharmacokinetics in patients undergoing hemodialysis has not been studied. Hepatic impairment: In patients with moderate hepatic impairment (Child-Pugh index from 7 to 9) the value of C max does not change, the AUC increased by 60%, t 1/2 doubles. The pharmacokinetics in patients with severe hepatic impairment has not been determined.
Treatment of Urge (mandatory), urinary incontinence, frequent urination and urgent (mandatory) urge to urinate, characteristic of patients with overactive bladder syndrome.
- urinary retention
- severe gastrointestinal diseases (including toxic megacolon)
- myasthenia gravis
- angle-closure glaucoma
- Hypersensitivity to the drug
- severe hepatic impairment
- severe renal impairment or moderate hepatic impairment, while the treatment of potent inhibitors of CYP3A4, such as ketoconazole
Before you begin treatment Vesicare should be established, there are other causes of frequent urination (heart failure or renal disease). If detected urinary tract infection, should start appropriate antibiotic treatment. Vesicare should be used with caution in patients:
- clinically significant obstruction with bladder outlet leading to the risk of urinary retention.
- with gastrointestinal obstructive disorders.
- with reduced risk of motility of the gastrointestinal tract.
- with severe renal impairment (creatinine clearance <30 mL per minute) and moderate hepatic (Child-Pugh index from 7 to 9) failure; dose for these patients should not exceed 5 mg.
- while receiving a potent inhibitor of CYP3A4, such as ketoconazole.
- with a hiatal hernia, gastroesophageal reflux disease, and in patients receiving both drugs (e.g., bisphosphonates) that may cause or exacerbate esophagitis.
- with autonomic neuropathy.
Patients with rare hereditary disorders of galactose tolerance, Lapp lactase deficiency (Sami), glucose-galactose malabsorption should not take the drug.
Pregnancy and lactation
No clinical data on women who became pregnant while taking solifenacin. Animal studies revealed no direct adverse effects on fertility, embryo / fetus or childbirth. Caution must be exercised in the appointment of the drug to pregnant women. There are no data on the excretion of solifenacin in human milk. The use of Vesicare is not recommended during breastfeeding.
Effects on ability to drive and operate machinery
Solifenacin, like other anticholinergics, can cause blurred vision, and (rarely) drowsiness and fatigue, which could adversely affect the ability to drive and use machines.
Dosing and Administration
5 mg once a day by mouth, some liquid, regardless of mealtime. If necessary, the dose may be increased to 10 mg once a day.
Vesicare can cause side effects associated with anticholinergic solifenacin, often mild or moderate severity. The frequency of these adverse effects depends on the dose. The most frequently reported side effect of Vesicare – dry mouth. It was observed in 11% of patients treated with a dose of 5 mg per day, 22% of patients treated with a dose of 10 mg per day, and 4% in the placebo group. Severity of dry mouth was generally mild and rarely led to discontinuation of treatment. In general, treatment adherence (compliance) was very high. The table below shows the other side effects reported in clinical studies, Vesicare:
|Common (> 1/100, <1/10)||Uncommon (> 1/1000, <1/100)||Rare (> 1/10000, <1/1000)|
|Violations of the gastrointestinal tract||constipation, nausea, dyspepsia, abdominal pain||gastroesophageal reflux disease, dry throat||Colonic obstruction, coprostasia|
|Infections and infestations||urinary tract infection|
|Disorders of the nervous system||somnolence, dysgeusia (taste disturbance)|
|Violations by the authorities of||blurred vision (disturbance of accommodation)||dry eyes|
|Violations of the general condition||fatigue, lower extremity edema|
|Violations of the respiratory, thoracic and mediastinal disorders||nasal dryness|
|Violations of the skin and subcutaneous tissue||xerosis|
|Violations of the kidney and urinary tract||difficulty urinating||urinary retention|
Allergic reactions winstrol reviews during clinical trials were not observed. However, the possibility of allergic reactions should not be excluded.
The highest dose of solifenacin that was used by volunteers was 100 mg as a single dose. At this dose, the most frequently observed following side effects: headache (mild), dry mouth (moderate), dizziness (mild), somnolence (mild) and blurred vision (moderate). No cases of acute overdose have been reported. In cases of overdose should be assigned to the activated carbon, gastric lavage, but do not induce vomiting. As in other cases of overdose of anticholinergic agents, symptoms to be treated as follows:
- in severe anticholinergic effects of central action (hallucinations, severe anxiety) – physostigmine or carbachol.
- in convulsions or severe irritability – benzodiazepines.
- with respiratory failure – artificial respiration.
- tachycardia – beta-blockers.
- at a delay of urination – catheterization.
- with mydriasis – instilled into the eyes of pilocarpine and / or place patient in dark room.
As in the case of an overdose of other anticholinergic drugs, special attention should be given to patients with established lengthening risk of QT interval (t. E. With hypokalemia, bradycardia, and while taking drugs that cause QT prolongation) and in patients with heart disease (myocardial ischemia, arrhythmia , congestive heart failure).
Interaction with other drugs
Pharmacological interactions Concomitant treatment with medicinal products with anticholinergic properties may result in more pronounced therapeutic and adverse effects. After winstrol reviews discontinuation of solifenacin should be done about a week break before starting treatment with another anticholinergic drug. The therapeutic effect may be reduced by simultaneous administration of cholinergic receptor agonists. Solifenacin can reduce the effect of drugs winstrall reviews that stimulate the motility of the gastrointestinal tract, for example – metoclopramide and cisapride.
Pharmacokinetic interaction studies in vitro showed that therapeutic concentrations solifenacin not inhibit CYP1A 1/2, 2C9, 2C19, 2D6, or ZA4 isolated from human liver microsomes. Therefore, it is unlikely that will change the drug solifenacin clearance metabolized by these CYP-enzymes. The effects of other drugs on the pharmacokinetics of solifenacin Solifenacin is metabolised of CYP3A4. Simultaneous administration of ketoconazole (200 mg daily), a potent inhibitor of CYP3A4, causing a twofold increase in AUC concentration vs. time solifenacin, and 400 mg / day – fold increase. Therefore Vesicare maximum dose should not exceed 5 mg, if the patient simultaneously receives ketoconazole or therapeutic doses of other strong CYP3A4 inhibitor (such as ritonavir, nelfinavir. Itraconazole). Simultaneous treatment of solifenacin and a potent inhibitor of CYP3A4 is contraindicated in patients with severe renal impairment or moderate winstrol reviews hepatic impairment. Since solifenacin metabolized by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (verapamil, diltiazem) and CYP3A4 inducers (rifampicin, phenytoin, carbamazepine).
Effect of solifenacin on the pharmacokinetics of other drugs Peroralnye contraceptives: There were no pharmacokinetic interaction of solifenacin and combined oral contraceptives (ethinyl estradiol \ levonorgestrel). Warfarin: Reception Vesicare did not cause changes in the pharmacokinetics of R-warfarin and S-warfarin or their effect on prothrombin time. Digoxin: Reception Vesicare no effect on the pharmacokinetics of digoxin. shop steroids cabaser dosage steroidwithdrawal.biz
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