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Viagra instructions and price in pharmacies Instruction prices Online Pharmacy analogs Prices in pharmacies Viagra - instructions for use Storage Indication Contraindication Dosage and administration Overdose Side effects Terms and conditions Use during pregnancy and lactation   Print Dosage Viagra tablet in / weaving. obol., 100 mg №1 (1x1) Manufacturer Fareva Amboise for "Pfizer Inc. ', France / USA Sildenafil INN Pharm. the group Drugs used in erectile dysfunction. Sildenafil. Registration number UA / 0313/01/03 dated 15.04.2013. Order number 300 of 04.15.2013 ATC code GZasoby operating urinary system and sex hormones G04Zasoby used in urology G04BInshi means used in urology, including antispasmodics G04BEZasoby used in erectile dysfunction G04BE03Syldenafil Viagra pill in / weaving. obol., 100 mg №1 (1x1) Storage Active ingredient: sildenafil; 1 tablet contains 70.225 mg of sildenafil citrate, which is equivalent to 50 mg of sildenafil; 1 tablet contains 140.450 mg of sildenafil citrate, which is equivalent to 100 mg of sildenafil; Additional ingredients: microcrystalline cellulose; anhydrous calcium hydrogen; croscarmellose sodium; magnesium stearate; Opadry® blue (OY-LS-20921): hypromellose; lactose monohydrate; glycerol triacetate; titanium dioxide (E 171); indigokarmina aluminum lacquer (E 132); Opadry® clear (YS-2-19114-A): hypromellose; glycerol triacetate. Dosage form Tablets, film coated tablets. Basic physical and chemical properties: tablets, film coated shell blue, diamond shaped with rounded edges, embossed «Pfizer» on one side and, according to the dosage, «VGR 50" or «VGR 100" - on the other. Pharmacotherapeutic group Drugs used in erectile dysfunction. Sildenafil. ATC Code G04B E03. Pharmacological properties Pharmacodynamics. The mechanism of action. Sildenafil is an oral drug designed to treat erectile dysfunction. When sexually aroused reduced drug restores erectile function by increasing blood flow to the penis. The physiological mechanism that causes an erection involves the release of nitric oxide (NO) in the cavernous bodies during sexual stimulation. Released nitric oxide activates the enzyme guanylate cyclase, which stimulates the increase of cyclic guanosine monophosphate (cGMP), which in turn causes relaxation of smooth muscles of the corpora cavernosa, promoting blood flow. Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase-5 (PDE5) in the cavernous bodies, where PDE5 is responsible for the decay of cGMP. Effects of sildenafil on erection are peripheral character. Sildenafil has no direct relaxing effect on isolated human cavernous body, but powerfully enhances the relaxing effect of NO on this tissue. When activated metabolic pathways NO / cGMP that occurs during sexual stimulation, inhibition of PDE5 sildenafil increases the levels of cGMP in the cavernous bodies. Thus, in order to sildenafil caused the desired pharmacological effect, you need sexual arousal. The impact on pharmacodynamics. Studies in vitro have shown that sildenafil is selective for PDE5, which is actively involved in the process of erection. The effect of sildenafil on PDE5 stronger than other known phosphodiesterase. This effect is 10 times stronger than the effect on FDE6 involved in the process of photoconversion in the retina. In applying the maximum recommended dose PDE5 selectivity of sildenafil to 80 times greater than its selectivity for FDE1, 700 times higher than FDE2, FDEZ, FDE4, FDE7, FDE8, FDE9, FDE10 and FDE11. In particular, sildenafil selectivity for PDE5 in 4000 times greater than its selectivity for FDEZ - cAMP-specific phosphodiesterase isoform involved in the regulation of cardiac contractility. Pharmacokinetics. Absorption. Sildenafil is rapidly absorbed. The maximum plasma drug concentrations are reached within 30-120 minutes (median of 60 minutes) after oral administration of glucose. The average absolute bioavailability after oral administration is 41% (with a range of values ​​from 25 to 63%). At the recommended dose range (25 to 100 mg) AUC and Cmax parameters of sildenafil after oral administration increased proportionally to the dose. When using sildenafil during a meal extent of absorption is reduced with a mean Tmax extension of up to 60 minutes and an average decrease in Cmax by 29%. Distribution. Average equilibrium volume of distribution (Vd) is 105 liters, indicating that the drug distribution in tissues. After a single oral administration of sildenafil 100 mg the average maximum total plasma concentration of sildenafil is approximately 440 ng / ml (coefficient of variation of 40%). Since binding Sildenafil and its main N-desmethyl-metabolite plasma proteins up to 96% mean maximum plasma concentration of sildenafil free up to 18 ng / mL (38 nmol). The degree of protein binding is independent of total concentration of sildenafil. In healthy volunteers, who once used sildenafil 100 mg, 90 minutes to ejaculate determined less 0.0002% (average 188 ng) of the applied dose. Biotransformation. Metabolism Sildenafil is mainly involving the liver microsomal isoenzymes CYP3A4 (major route) and CYP2C9 (minor route). The main circulating metabolite formed by N-demethylation of sildenafil. Selectivity metabolite relatively PDE5 selectivity comparable to sildenafil and the metabolite activity relative PDE5 approximately 50% of the activity of the starting material. Plasma concentrations of this metabolite are approximately 40% concentration in plasma sildenafil. N-demetylovanyy metabolite undergoes further metabolism, and during its half-life is about 4 hours. The elimination. The total clearance of sildenafil is 41 l / h, causing its half-life period lasting 3-5 hours. As after oral and after intravenous administration of sildenafil excretion as metabolites is mainly with feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered oral dose). Pharmacokinetics in special patient groups. Elderly patients. In healthy elderly volunteers (aged 65), a decrease of sildenafil clearance that led to increase plasma concentrations of sildenafil and its active metabolite N-demetylovanoho about 90% compared with the corresponding concentrations in healthy younger volunteers (18-45 years). Due to age-related differences in binding to plasma proteins corresponding increase in free sildenafil plasma concentration was approximately 40%. Kidney failure. In volunteers with renal impairment mild to moderate (creatinine clearance 30-80 ml / min), sildenafil pharmacokinetics remain unchanged after a single oral dose of 50 mg. Mean AUC and Cmax N-demetylovanoho metabolite were increased by 126% and 73%, respectively, compared with rates in volunteers of similar age without renal dysfunction. However, because of the high individual variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance below 30 ml / min), sildenafil clearance was reduced, resulting in increases in AUC and medium Cmax of 100% and 88% respectively compared to volunteers of similar age without renal dysfunction. In addition, the value of AUC and Cmax N-demetylovanoho metabolite were increased significantly by 79% and 200% respectively. Liver failure. In volunteers with hepatic cirrhosis mild to moderate (Class A and B classification Child-Pugh) sildenafil clearance was reduced, leading to an increase in AUC (84%) and Cmax (47%) compared to volunteers of similar age without dysfunction liver. The pharmacokinetics of sildenafil in patients with impaired liver function severe not been studied. Indication Viahra® drug is recommended for men with erectile dysfunction, which is defined as the inability to achieve or maintain penile erection necessary for successful sexual intercourse. For effective action of the drug Viahra® desired sexual arousal. Contraindication Hypersensitivity to the active substance or any of the excipients of the drug. Concomitant use of nitric oxide donors (such as amyl nitrite) or nitrates in any form is contraindicated, since it is known that sildenafil affects the way the metabolism of nitric oxide / cyclic guanosine monophosphate (cGMP) and potentiates the hypotensive effect of nitrates. The conditions under which sexual activity is not recommended (eg severe cardiovascular disorders such as unstable angina or heart failure, severe). Loss of vision in one eye because of nearterialnoyi anterior ischemic optic neuropathy regardless of whether the condition is associated with previous PDE5 inhibitors or not. The presence of diseases such as liver dysfunction severe, hypotension (blood pressure below 90/50 mm Hg. In.), Recently transferred stroke or myocardial infarction and known hereditary degenerative retinal diseases such as retinitis pigmentosa (a small number of such patients has disorders of retinal phosphodiesterases genetic), because safety of sildenafil has not been investigated in these subgroups. Interaction with other medicinal products and other forms of interaction Effects of other medicinal products on sildenafil. viagra professional vs viagra super active Studies in vitro. Metabolism Sildenafil is primarily via ZA4 isoforms (main road) and isoforms 2C9 (minor route) cytochrome P450 (CYP). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance. Studies in vivo. Population pharmacokinetic analysis of clinical studies has demonstrated reduction in sildenafil clearance at its simultaneous application with inhibitors of CYP3A4 (such as ketoconazole, erythromycin, cimetidine). Although the concomitant use of sildenafil and CYP3A4 inhibitors increase the frequency of adverse events was observed, should consider taking an initial dose of 25 mg sildenafil. Concomitant use of HIV protease inhibitors ritonavir, a potent inhibitor of P450 in a state of equilibrium concentration (500 mg 1 time per day) and sildenafil (single dose 100 mg) resulted in the increase of Cmax of sildenafil 300% (4 times) and increase plasma AUC sildenafil 1000% (11 times). After 24 hours, plasma levels of sildenafil were still approximately 200 ng / ml, compared with a level of about 5 ng / ml, typical for the use of sildenafil alone responsible ritonavir significant impact on a wide range of substrates P450. Sildenafil has no effect on ritonavir pharmacokinetics. Given these pharmacokinetic data concomitant use of sildenafil and ritonavir is not recommended (see. Section "Peculiarities of Application"); in any event the maximum dose of sildenafil in no circumstances exceed 25 mg within 48 hours. Concomitant use of HIV protease inhibitors saquinavir, an inhibitor of CYP3A4, at a dose that provides equilibrium concentration (1200 mg three times a day) and sildenafil (100 mg single) led to an increase in Cmax of sildenafil in 140% and an increase in systemic exposure (AUC) of sildenafil in 210%. There was no impact on sildenafil pharmacokinetics of saquinavir (see. Section "Dosage and Administration"). It is assumed that more potent inhibitors of CYP3A4, such as ketoconazole and itraconazole, will have a more pronounced effect. When using sildenafil (100 mg single) and erythromycin, a moderate inhibitor of CYP3A4, at steady state (500 mg twice daily for 5 days) was observed increase in systemic exposure to sildenafil 182% (AUC). In healthy male volunteers there was no influence of azithromycin (500 mg daily for 3 days) on the AUC, Cmax, Tmax, elimination rate constant and the subsequent half-life of sildenafil or its principal circulating metabolite. Cimetidine (an inhibitor of cytochrome P450 and a nonspecific inhibitor of CYP3A4) at a dose of 800 mg with concomitant use of sildenafil 50 mg in healthy volunteers resulted in an increase of sildenafil plasma concentrations by 56%. Grapefruit juice is a weak inhibitor of CYP3A4 in the intestinal wall and can cause moderate increase in levels of sildenafil in the blood plasma. Single use of antacid (magnesium hydroxide / aluminum hydroxide) did not affect the bioavailability of sildenafil. Although studies of specific interaction with all drugs was conducted, according to the population pharmacokinetic analysis, the pharmacokinetics of sildenafil has not changed in its concomitant use of drugs belonging to the group of inhibitors of CYP2C9 (tolbutamide, warfarin, phenytoin), a group of inhibitors of CYP2D6 (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and tiazydopodibnyh of diuretics, loop and potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, calcium antagonists, β-adrenoceptor antagonists or inducers of CYP450 metabolism (such as rifampicin, barbiturates). viagra professional vs viagra super active In a study involving healthy volunteers male simultaneous application antagonist of endothelin bosentanu (moderate inducer of CYP3A4, CYP2C9 and possibly, CYP2C19) at steady state (125 mg twice daily) and sildenafil at steady state (80 mg three times daily) resulted in decrease in AUC and Cmax of sildenafil in 62.6% and 55.4% respectively. Therefore, concomitant use of strong inducers of CYP3A4, as rifampin, can result in a more pronounced reduction in the concentration of sildenafil in plasma. Nikorandyl is a hybrid calcium channel activator and nitrate. Nitrate component determines the possibility of serious interaction with sildenafil. Effects of sildenafil on other medicinal products. Studies in vitro. Sildenafil - a weak inhibitor isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and ZA4 cytochrome P450 (IC50> 150 mmol). Since sildenafil peak plasma concentrations are equal to about 1 mmol, Viahra® effect of the drug on the clearance of substrates of these isoenzymes unlikely. There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors like dipyridamole and theophylline. Studies in vivo. Since it is known that sildenafil has an effect on the metabolism of nitric oxide / cyclic guanosine monophosphate (cGMP), it was found that sildenafil potentiates the hypotensive effect of nitrates, so its simultaneous use with donors of nitric oxide or nitrates in any form is contraindicated (see. Section " Contraindication"). Concomitant use of sildenafil and α-adrenergic blockers may lead to symptomatic hypotension in some patients predisposed to it. This reaction often occurred within 4 hours after use of sildenafil (see. Section "Dosage and Administration" and "Peculiarities of Application"). In the 3 studies specific interaction of drugs blocker α-blockers doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) were used simultaneously to patients with benign prostatic hyperplasia, stabilization which was achieved by the use of doxazosin. In these populations experienced an average additional reduction in blood pressure in the supine position at 7/7 mmHg. Art., 9.5 mm Hg. Art. and 8/4 mm Hg. Art. and the average reduction in blood pressure on standing 6/6 mmHg. Art., 11/4 mmHg. Art., 4/5 mmHg. Art. in accordance. Concomitant administration of sildenafil and doxazosin in patients whose stabilization was achieved in the application of doxazosin, sometimes reported the development of symptomatic orthostatic hypotension. These reports dealt with the cases of dizziness and fainting to the state, but not syncope. There was not any significant interactions with the concomitant use of sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg), which is metabolized CYP2C9. viagra professional vs viagra super active Sildenafil (50 mg) did not result in prolongation of bleeding time caused by the use of aspirin (150 mg). Sildenafil (50 mg) were potentsiyuvav hypotensive effects of alcohol in healthy volunteers with mean maximum blood ethanol levels of 80 mg / dl. Patients who used sildenafil, was not observed any differences in side effect profile compared to placebo, while the application of such classes of antihypertensive drugs as diuretics, blockers, β-blockers, ACE inhibitors, antagonists of angiotensin II, antihypertensive medicinal products (vasodilator and centrally acting) blockers adrenergic neurons, calcium channel blockers and α-blockers. In a special study of the interaction with concomitant use of sildenafil (100 mg) and amlodipine in patients with hypertension was observed additional reduction in systolic blood pressure in the supine position on 8 mm Hg. Art.

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