Viagra 100 mg (1 tablet)

The instruction for medical use of VIAGRA® medicine the Trade name of Viagra® the International unlicensed name Sildenafil Lekarstvennaya the Tablet form, film coated 50 mg, 100 mg Structure One tablet contains active agent - sildenafit citrate of 70.225 mg and 140.450 mg (it is equivalent to a sildenafil of 50 mg and 100 mg), excipients: microcrystalline cellulose, calcium hydrophosphate anhydrous, sodium of a kroskarmelloz, magnesium stearate, Structure of a cover: opadray blue OY-LS-20921 (a gipromelloza, lactose, triacetin, the titan dioxide (E 171) and indigo carmine aluminum varnish (E132)), opadray transparent YS-2-19114 A (gipromelloza and triacetin) the Description of the Tablet, film coated, blue color biconvex, in the form of the rounded-off rhombus with marking of Pfizer on one and VGR 50 (for a dosage of 50 mg) or VGR 100 (for a dosage of 100 mg), on other party. Pharmacotherapeutic group Drugs for treatment of urological diseases. Other drugs for treatment of urological diseases, including spasmolysants. Drugs for treatment of disturbances of an erection. Sildenafil. ATH G04BE03 code sildenafit the Pharmacological Pharmacokinetics Absorption Later properties of intake quickly is soaked up. The maximum concentration (Cmax) of a sildenafil in blood plasma are reached during the period from 30 to 120 minutes (median of 60 minutes) after oral administration on an empty stomach. The average absolute bioavailability at oral administration of drug is 41% (with a range of values of 25 - 63%). After oral administration of a sildenafil in the recommended range of doses (25 - 100 mg) of value of the area under pharmacokinetic curve (AUC) and Cmax raise in direct ratio to the accepted dose. At reception of a sildenafil with food the speed of absorption decreases with an average delay of time of achievement of the maximum concentration in blood plasma (tmax) of 60 minutes and average reduction of Cmax value by 29%. Distribution the Average equilibrium volume of distribution (Vd) for a sildenafil makes 105 l that demonstrates its distribution in body tissues. After oral administration of a sildenafil in a single dose of 100 mg the average maximum general concentration of a sildenafil in blood plasma makes about 440 ng/ml (with the coefficient of variation of 40%). Because sildenafit (and its main circulating metabolite - a N-desmetil-metabolite) for 96% contacts proteins of blood plasma, average maximum concentration of a free sildenafil in blood plasma makes 18 ng/ml (38 nanometers). Linking with proteins does not depend on the general concentration of drug. At the healthy volunteers receiving sildenafit once in a dose 100 mg, in 90 minutes after reception of a dose in an ejaculate less than 0.0002% (on average - 188 ng) the accepted drug dose were defined. Metabolism of the Research in vitro Metabolism of a Sildenafil is carried out mainly with the participation of microsomal isoenzymes of a liver of CYP3A4 (main way) and CYP2C9 (minor way) of P450 cytochrome. By N-demethylation the main circulating metabolite of a sildenafil which is exposed to further metabolism with final elimination half-life is formed, components are about 4 hours old. The metabolite is characterized by a selectivity profile to phosphodiesterase, comparable to that sildenafit, and the activity of a metabolite of in vitro in relation to phosphodiesterase of the 5th type (FDE-5) is about 50% of activity of initial substance of drug. Concentration of this metabolite in blood plasma make about 40% of concentration of a sildenafil. Removal the General clearance of a sildenafil makes 41 l/h, and final elimination half-life from 3 to 5 hours. After oral administration sildenafit it is removed in the form of metabolites generally with excrements (about 80% of the accepted oral dose) and to a lesser extent with urine (about 13% of an oral dose). Pharmacokinetics at special groups of patients Patients of advanced age At healthy volunteers of advanced age (at the age of 65 years or is more senior) the decrease in clearance of a sildenafil was noted, causing increase in concentration in plasma of a sildenafil and its active N-demetilirovannogo of a metabolite approximately for 90% in comparison with those at healthy volunteers of younger age (18-45 years). Due to the age differences in binding of proteins of blood plasma, the corresponding increase in concentration of a free sildenafil in blood plasma is about 40%. Patients with a renal failure At patients with easy or moderate degree of a renal failure (clearance of creatinine of 30-80 ml/min.) the pharmacokinetics of a sildenafil after single oral administration in a dose of 50 mg does not change. Increase in average values of AUC and Cmax N-demetilirovannogo of a metabolite was up to 126% and up to 73% respectively in comparison with such indicators at people of similar age without renal failures. However in connection with high variability of indicators between patients these differences were not significant. At patients with heavy renal failures (clearance of creatinine & lt, 30 ml/min.) the clearance of a sildenafil decreased that led to average increases in indicators of AUC and Cmax, respectively for 100% and 88% in comparison with patients of similar age without renal failures. Besides, AUC and Cmax values for metabolite N-demetilirovannogo also considerably increased - by 200% and 79%, respectively. Patients with an abnormal liver function the patients with cirrhosis of light and moderate severity (stages And yes In on classification of Chayld-Pyyu) had a reduced clearance of a sildenafil that also Cmax (for 47% led to increase in indicators of AUC (for 84%)) in comparison with volunteers of similar age without disturbances of functions of a liver. The pharmacokinetics of a sildenafil at patients with heavy degree of an abnormal liver function was not studied. The pharmacodynamics the Mechanism of action Viagra®, oral medicine for treatment of erectile dysfunction, that is at sexual stimulation, it restores the broken erectile function by increase in inflow of blood to a penis. The physiological mechanism of an erection of a penis includes release of nitrogen oxide (NO) in cavernous bodies at sexual stimulation. Nitrogen oxide activates enzyme guanylate cyclase that leads to increase in levels of the cyclic guanozinmonofosfat (tsGMF), the subsequent relaxation of smooth muscles in cavernous bodies and to increase in inflow of blood. Sildenafil is strong and selection inhibitor of tsGMF-specific phosphodiesterase of the 5th type (FDE-5) which is responsible for disintegration of tsGMF in cavernous bodies. Sildenafil has peripheral effect on an erection. Sildenafil has no direct weakening effect on the isolated cavernous human body, but considerably enhances the weakening effect NO on this fabric. At activation of a metabolic way NO/tsGMF as it occurs during sexual stimulation, FDE-5 inhibition sildenafily leads to increase in the tsGMF levels in cavernous bodies. Therefore sexual stimulation is necessary for rendering sildenafily desirable productive pharmacological action. Pharmakodinamichesky effects of the Research in vitro Sildenafil selectively acts on FDE-5 which participates in regulation of process of an erection. Action of Viagry® Is one FDE-5 stronger, than on other known phosphodiesterases. This effect of action of Viagry® is 10 times stronger, than effect on FDE-6 which takes part in processes of phototransformation in an eye retina. At use in the maximum recommended doses the selectivity of a sildenafil to FDE-5 by 80 times exceeds its selectivity to FDE-1, more than by 700 times - selectivity to FDE-2, FDE-3, FDE-4, FDE-7, FDE-8, FDE-9, FDE-10 and FDE-11. In particular, the selectivity of a sildenafil to FDE-5 by 4000 times exceeds its selectivity to FDE-3 - a tsAMF-specific isoform of the phosphodiesterase which is taking part in regulation of warm reductions. Clinical performance and safety Safety and efficiency of a sildenafil were confirmed with data of long-term researches. Indications - the erectile dysfunction which is characterized by inability to achievement or preservation of an erection of a penis sufficient for satisfactory sexual intercourse. Виагра® it is effective only at sexual stimulation. A route of administration and doses For oral administration. Виагру® it is possible to accept with food or without. Nevertheless, to start action of Viagry® more time in case of reception with food can be necessary. The dosing mode Use for adults the Recommended dose of Viagry® makes 50 mg inside approximately in 1 hour prior to sexual intercourse. Taking into account efficiency and shipping the dose can be increased up to 100 mg. The maximum recommended dose makes 100 mg. It is necessary to swallow a tablet entirely, washing down with a glass of water. The maximum recommended reception frequency - 1 time a day. Special groups of patients Patients of advanced age (≥ 65 years) dose adjustment is not required From patients of advanced age. Patients with a renal failure At easy and moderate degree of a renal failure (clearance of creatinine of 30-80 ml/min.) the dose adjustment is not required. Due to the decrease in clearance of a sildenafil at patients with a heavy renal failure (clearance of creatinine & lt, 30 ml/min.), it is necessary to consider the possibility of use of Viagry® in a dose of 25 mg. Proceeding from efficiency and tolerance of drug if necessary, it is possible to increase its dose step by step to 50 mg and up to 100 mg. Patients with an abnormal liver function Because the clearance of a sildenafil is lowered at patients with an abnormal liver function (for example, cirrhosis), it is necessary to consider the possibility of use of drug in a dose of 25 mg. Proceeding from efficiency and tolerance of drug if necessary, it is possible to increase its dose step by step to 50 mg and up to 100 mg. Patients of children's and teenage age Sildenafil is not shown for use for children (& lt, 18 years). Use for the patients accepting other medicines except for a ritonavir which is not recommended to be accepted along with sildenafily it is necessary to consider the possibility of use of drug in an initial dose of 25 mg at the patients receiving the accompanying therapy by CYP3A4 inhibitors. For the purpose of reduction of risk of development of postural arterial hypotension in the patients undergoing treatment by alpha adrenoblockers it is necessary to stabilize a condition of the patients receiving alpha adrenoblockers before beginning treatment sildenafily. Besides, it is necessary to consider the possibility of use of a sildenafil, since a dose of 25 mg. Side effects by the Most frequent undesirable reactions are a headache, hyperaemia, dyspepsia, congestion of a nose, dizziness, nausea, inflows, a disorder of vision, blue vision and indistinct sight. At use of Viagry®, undesirable effects which were classified by the frequency of their manifestation as follows are registered: very often (≥ 1/10), it is frequent (from ≥ 1/100 to & lt, 1/10), infrequently (from ≥ 1/1000 to & lt, 1/100) and is rare (≥ 1/10,000 and & lt, 1/1000). Very often - a headache Often - dizziness - color distortions of sight (chloropsiya, a chromatopsia, blue vision, red vision, a xanthopsia), a visual disturbance, illegibility of sight - hyperaemia, inflows - congestion of a nose - nausea, dyspepsia Infrequently - rhinitis - hypersensitivity - drowsiness, a hypesthesia - the disturbances connected with dacryagogue (xerophthalmus, dysfunction of a lacrimal gland, the raised dacryagogue), eye pain, photophobia, a photopsia, hyperaemia of vessels of eyes, brightness of visual perception, conjunctivitis - a spatial disorientation (vertigo), sonitus - tachycardia, heart consciousness - arterial hypertension, arterial hypotension - nasal bleeding, congestion of adnexal bosoms of a nose - a gastroesophageal reflux disease, vomiting, pain in an upper part of a stomach, dryness in a mouth - rash - myalgia, extremity pain - a hamaturia - thorax pain, increased fatigue, feeling of heat - the increased heart rate Seldom - an acute disorder of cerebral circulation, the tranzitorny ischemic attack, a convulsive attack *, a recurrence of a convulsive attack *, a syncope - front nearteriitny ischemic neuropathy of an optic nerve *, occlusion of vessels of a retina *, a retinal apoplexy, an arteriosclerotic retinopathy, a retina disease, glaucoma, defect of a field of vision, a diplopia, decrease in visual acuity, shortsightedness, an asthenopia, vitreous floating opacities, a disease of an iris of the eye, a mydriasis, existence in sight of iridescent circles, eye hypostasis, swelling of an eye, a visual disturbance, conjunctival hyperaemia, irritation of an eye, unusual feeling in an eye, swelled a century, discoloration of a sclera - deafness - a sudden cardiac death *, a myocardial infarction, ventricular arrhythmia *, fibrillation of auricles, unstable stenocardia - feeling of constraint in a throat, nose hypostasis, dryness mucous a nose - an oral hypesthesia - Stephens's syndrome - Johnson *, a toxic epidermal necrolysis * - bleeding from a penis, a priapism *, a gematospermiya, strengthening of an erection - irritability * the side effects registered only during post-registration observation. The message of data on expected undesirable reactions the Message of data on the expected undesirable reactions revealed after medicine registration is of great importance. It allows to continue monitoring of a ratio of advantage and risk of medicine. Health workers and patients are asked to report about any undesirable reactions to the address specified at the end of this instruction for medical use. Contraindications - hypersensitivity to active agent or to any of excipients - a concomitant use of drugs, being donators of nitrogen oxide (amyle nitrite) or nitrates in any form - a concomitant use with guanylate cyclase stimulators (riotsiguat) - a heavy liver failure - hereditary degenerative diseases of a retina of an eye (for example, a hereditary pigmentary retinitis (the small number of these patients has inherited disorders of functions of phosphodiesterases of a retina)) - loss of sight on one eye owing to front nearteriitny ischemic neuropathy of an optic nerve, regardless of whether this episode was connected with the previous use of FDE-5 inhibitor or not - arterial hypotension (the ABP & lt, 90/50 mm Hg.) - a serious cardiovascular illness (for example, heavy heart failure, unstable stenocardia) - the myocardial infarction postponed to the last 6 months - the stroke which is had in the last 6 months - to men with rare hereditary intolerance of a galactose, deficiency of Lappa lactase or a sprue of glucose and a galactose On the registered indication drug is not intended for use for children and teenagers aged up to 18 years and at women. Medicinal interactions Influence of other medicines on sildenafit the Researches in vitro Metabolism of a Sildenafil it is generally mediated by isoforms 3A4 (main way) and 2C9 (a minor way) P450 (CYP) cytochrome. For this reason inhibitors of these isoenzymes can reduce, and inductors of these isoenzymes - to increase clearance of a sildenafil. The researches in Vivo At a concomitant use of a sildenafil with CYP3A4 inhibitors (such as ketokonazol, erythromycin and Cimetidinum) decrease in clearance of a sildenafil is observed. At this group of patients the increased frequency of side effects is not observed, nevertheless, it is necessary to begin the Viagra® drug treatment in an initial dose of 25 mg. The concomitant use of inhibitor of HIV protease of the ritonavir which is strong inhibitor of P450 cytochrome in an equilibrium state (two times a day) with sildenafily (100 mg a single dose) leads 500 mg to increase in the maximum concentration (Cmax) in a sildenafil by 300% (4-hkratno) and also to increase in AUC of a sildenafil in blood plasma for 1000% (11-multiply). In 24 hours the levels of a sildenafil in blood plasma are about 200 ng/ml in comparison with about 5 ng/ml after reception only sildenafit. These data will be agreed with the significant effects of a ritonavir on a wide range of substrates of P450 cytochrome. Based on the above-stated data, simultaneous use of a sildenafil with ritonaviry is not recommended. Виагра® does not influence pharmacokinetics of a ritonavir. The maximum dose sildenafit at any obstoyatelst
ah should not exceed 25 mg within 48 hours. The concomitant use of inhibitor of HIV protease of the sakvinavir which is CYP3A4 inhibitor in an equilibrium state (three times a day) with sildenafily (100 mg a single dose) leads 1200 mg to increase in Cmax of a sildenafil by 140% and also increase in AUC of a sildenafil by 210%. Sildenafil does not influence pharmacokinetics of a sakvinavir. Stronger CYP3A4 inhibitors, such as ketokonazol and itrakonazol, have more significant effect. At single dose of a sildenafil in a dose of 100 mg together with the erythromycin moderated by CYP3A4 inhibitor in an equilibrium state (500 mg two times a day within 5 days), increase in system influence of a sildenafil by 182% is observed (is determined by
the Develop value AUC). & am