Sildenafil Citrate

Instructions for use of Viagra

Brand-acting substance Conditions of release from the pharmacy Composition and form of release Description of the dosage form Pharmacological action Pharmacokinetics Pharmacodynamics Indications for use It is recommended that contraindications sildenafil citrate to use are used during pregnancy and child-side effects Drug interaction overdose overdose precautions.

Brand
Viagra
Active substance
Sildenafil*
Conditions of release from pharmacies
By prescription
Composition and form of release
Tablets - 1 tab.:

Active substance: Sildenafil 50 mg in the form of sildenafil citrate 70,225 mg;
Excipients: ludiflesh 343.525 mg (contains mannitol ~ 302.30 mg, crospovidone ~ 17.18 mg, polyvinyl acetate ~ 16.32 mg, povidone ~ 1.46 mg), croscarmellose sodium 25,000 mg, microcrystalline cellulose 25,000 mg, colloidal silicon dioxide 3,750 mg, sucralose 5,000 mg, indigocarmine (30-36%) 2,500 mg, sweetener (Sweetness Enhancer) 5,000 mg (contains maltodextrin 3,565 mg, flavor 0.790 mg, dextrin 0.395 mg, residual water 0.250 mg), Natural flavor (Natural Special) 5,000 mg (contains maltodextrin 4,300 mg, propylene glycol 0.185 mg, glycerol 0.180 mg, flavor 0.085 mg, residual water 0.250 mg), lemon Flavor 5,000 mg (contains maltodextrin 40000 mg, flavor 0.7500 mg, alpha-tocopherol 0.0003 mg, residual water 0.2500 mg), magnesium stearate 10,000 mg.
4 tablets in a blister of PA/Aluminum/IIBX film and aluminum foil.

1 blister along with instructions for use in a cardboard pack.

A perforated control line of the first opening is applied to the front side of the cardboard pack.

The protective sticker is located in the right upper corner of the back surface of the pack.

Description of the dosage form
The tablets are blue, diamond-shaped with the engraving "V50" on one side and smooth on the other side.

Pharmacological action
The treatment for erectile dysfunction is a PDE5 inhibitor.

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 maximum 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: Cmax decreases by an average of 29%, and the time to reach the maximum concentration (Tmax) increases by 60 minutes, but 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 about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose of sildenafil (on average 188 ng) was detected in semen 90 minutes after taking the drug.

Metabolism

Sildenafil is metabolized mainly in the liver under the action of cytochrome CYP3A4 isoenzyme (main pathway) and cytochrome CYP2C9 isoenzyme (minor 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 (over 65 years old), 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 old). Age does not have a clinically significant effect on the incidence of side effects.

Impaired renal function

With mild (creatinine clearance (CC) 50-80 ml / min) and moderate (CC 30-49 ml / min) degree of renal insufficiency, the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change.

In severe renal insufficiency (CC < 30 ml/min), the clearance of sildenafil decreases, which leads to an approximately twofold increase in AUC (100%) and Cmax (88%) compared with those in normal renal function in patients of the same age group.

Liver function disorders

In patients with cirrhosis of the liver (classes A and B according to the Child-Pugh classification), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age group.

The pharmacokinetics of sildenafil in patients with severe hepatic impairment (Child-Pugh class C) has not been studied.

Pharmacodynamics
Sildenafil is a powerful selective inhibitor of cycloguanosine 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 PDE3, which is of crucial importance, since PDE3 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 tadalafil 20mg 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 was 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 others medicines").

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 the 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 impairment

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 the drug, 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.