Description

Treatment of erectile dysfunction characterized by an inability to achieve or maintain a penile erection sufficient for satisfactory intercourse
Sildenafil is only effective in the presence of sexual stimulation.

Specifications
Active ingredients of Sildenafil
The form of the release of the film-coated tablets, 100 mg – 1 pc. per pack.
Country of Productionrussia
Productionozon LLC
Store in a place protected from light
Keep away from children
Dosage form
Round biconvex tablets covered with a blue film coating. Two layers are visible on the cross section of the tablet: the core is white or almost white in color and the shell.
Composition
Per tablet:
Active ingredient: sildenafil citrate – 140,4800 mg (in terms of sildenafil base – 100,0000 mg).
Excipients: lactose monohydrate (milk sugar) – 120.0000 mg, microcrystalline cellulose – 87.7200 mg, sodium croscarmellose – 16.0000 mg, povidone-K25 – 12.0000 mg, magnesium stearate – 3.8000 mg.
Shell composition: opadray II 85F205024 blue – 12.0000 mg, including: polyvinyl alcohol – 4.8000 mg; macrogol-4000 – 2.4240 mg; aluminum varnish with indigocarmine and diamond blue dyes – 0.7476 mg; iron oxide yellow dye – 0.0324 mg; talc – 1.7760 mg; titanium dioxide – 2.2200 mg.
Pharmacotherapeutic group
erectile dysfunction treatment – PDE5-inhibitor
Pharmacodynamics
Sildenafil is a powerful selective inhibitor of cyclic guanosine monophosphate (cGMP)- specific phosphodiesterase type 5 (PDE5).
Mechanism of action
The realization of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, [subsequent relaxation of the smooth muscle tissue of the cavernous body and an increase in blood flow.
Sildenafil does not have a direct relaxing effect on the isolated human cavernous body, but enhances the effect of nitric oxide (NO) by inhibiting PDE5, which is responsible for the breakdown of cGMP.
Sildenafil is selective against PDE5 in vitro, its activity against PDE5 exceeds the activity against other known phosphodiesterase isoenzymes: PDE6 – 10 times; PDE1 – more than 80 times; PDE2, PDE4. PDE7-PDE11 – more than 700 times. Sildenafil is 4000 times more selective against PDE5 compared to PDEZ, which is of crucial importance, since PDEZ is one of the key enzymes regulating myocardial contractility.
A prerequisite for the effectiveness of sildenafil is sexual stimulation. Sildenafil restores impaired erectile function under conditions of sexual stimulation by increasing blood flow to the cavernous bodies of the penis.
Clinical data
Cardiological studies
The use of sildenafil in doses up to 100 mg did not lead to clinically significant ECG changes in healthy volunteers. The maximum decrease in systolic pressure in the supine position after taking sildenafil at a dose of 100 mg was 8.3 mmHg, and diastolic pressure – 5.3 mmHg. A more pronounced, but also transient effect on blood pressure (BP) was observed in patients taking nitrates (see sections “Contraindications” and “Interaction with other drugs”).
In a study of the hemodynamic effect of sildenafil in a single dose of 100 mg in 14 patients with severe coronary artery disease (CHD) (more than 70% of patients had stenosis of at least one coronary artery), systolic and diastolic pressure at rest decreased by 7% and 6%, respectively, and pulmonary systolic pressure decreased by 9%. Sildenafil did not affect cardiac output and did not disrupt blood flow in stenosed coronary arteries, and also led to an increase (by about 13%) in adenosine-induced coronary flow in both stenosed and intact coronary arteries.
In a double-blind placebo-controlled study, 144 patients with erectile dysfunction and stable angina taking antianginal drugs (except nitrates) performed physical exercises until the severity of angina symptoms decreased. The duration of the exercise was significantly longer (19.9 seconds; 0.9-38.9 seconds) in patients taking sildenafil in a single dose of 100 mg compared with patients receiving placebo.
In a randomized, double-blind, placebo-controlled study, the effect of changing the dose of sildenafil (up to 100 mg) was studied in men (n=568) with erectile dysfunction and hypertension taking more than two antihypertensive drugs. Sildenafil improved erection in 71% of men compared to 18% in the placebo group. The frequency of adverse effects was comparable to that in other groups of patients, as well as in those taking more than three antihypertensive drugs.
Studies of visual disorders
In some patients, 1 hour after taking sildenafil at a dose of 100 mg, a slight and transient impairment of the ability to distinguish shades of color (blue / green) was detected using the Farnsworth-Munsel 100 test. 2 hours after taking sildenafil, these changes were absent. It is believed that color vision impairment is caused by inhibition of PDE6, which is involved in the process of light transmission in the retina of the eye. Sildenafil had no effect on visual acuity, contrast perception, electroretinogram, intraocular pressure or pupil diameter.
In a placebo-controlled cross-sectional study of patients with proven early-age macular degeneration (n=9), sildenafil in a single dose of 100 mg was well tolerated. There were no clinically significant changes in vision assessed by special visual tests (visual acuity, Amsler lattice, color perception, color passage modeling, Humphrey perimeter and photostress).
Effectiveness
The efficacy and safety of sildenafil were evaluated in 21 randomized, double-blind, placebo-controlled trials lasting up to 6 months in 3,000 patients aged 19 to 87 years, with erectile dysfunction of various etiologies (organic, psychogenic or mixed).
The effectiveness of the drug was evaluated globally using an erection diary, an international index of erectile function (a validated questionnaire on the state of sexual function) and a partner survey. The efficacy of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory sexual intercourse, has been demonstrated in all studies conducted and has been confirmed in long-term studies lasting 1 year. In fixed-dose studies, the ratio of patients who reported that therapy improved their erection was: 62% (sildenafil 25 mg dose), 74% (sildenafil 50 mg dose) and 82% (sildenafil 100 mg dose) compared with 25% in the placebo group. The analysis of the international index of erectile function showed that in addition to improving the erection, treatment with sildenafil also increased the quality of orgasm, allowed to achieve satisfaction from sexual intercourse and general satisfaction.
According to the generalized data, 59% of diabetic patients, 43% of patients who underwent radical prostatectomy and 83% of patients with spinal cord injuries reported an improvement in erection during treatment with sildenafil (versus 16%, 15% and 12% in the placebo group, respectively).
Pharmacokinetics
The pharmacokinetics of sildenafil in the recommended dose range is linear.
Suction
After ingestion, sildenafil is rapidly absorbed. Absolute bioavailability averages about 40% (from 25% to 63%). In vitro, sildenafil at a concentration of about 1.7 ng/ml (3.5 nM) suppresses human PDE5 activity by 50%. After a single dose of sildenafil at a dose of 100 mg, the average facsimile concentration of free sildenafil in the blood plasma (Cmax) of men is about 18 ng /ml (38 nM). Cmax when taking sildenafil inside on an empty stomach is achieved on average within 60 minutes (from 30 minutes to 120 minutes). When taken in combination with fatty foods, the absorption rate decreases: the Cmax decreases by an average of 29%, and the time to reach the maximum concentration (Tmax) increases by 60 minutes. however, the degree of absorption does not significantly change (the area under the pharmacokinetic concentration-time curve (AUC) decreases by 11%).
Distribution
The volume of distribution of sildenafil in the equilibrium state is on average 105 liters.
The association of sildenafil and its main circulating N-demethyl metabolite with plasma proteins is approximately 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose (on average 188 ng) was detected in semen 90 minutes after taking sildenafil.
Metabolism
Sildenafil is metabolized mainly in the liver under the action of cytochrome P450 CYP3A4 system isoenzyme (main pathway) and cytochrome P450 CYP3A4 CYP2C9 system isoenzyme (additional pathway). The main circulating active metabolite formed as a result of N-demethylation of sildenafil undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of sildenafil, and its activity against PDE5 in vitro is about 50% of the activity of sildenafil. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further metabolism; its half-life (T1/2) is about 4 hours.
Withdrawal
The total clearance of sildenafil is 41 liters / hour, and the final T1/2 is 3-5 hours. After oral administration, as well as after intravenous administration, sildenafil is excreted as metabolites, mainly by the intestine (about 80% of the oral dose) and, to a lesser extent, by the kidneys (about 13% of the oral dose).
Pharmacokinetics in special groups of patients
Elderly patients
In healthy elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of free sildenafil in blood plasma is about 40% higher than in young (18-45 years). Age does not have a clinically significant effect on the incidence of side effects.
Impaired renal function

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